bims-bac4me 2023-08-13 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023‒08‒13
thirty-two papers selected by
Chun-Chi Chang
University Hospital Zurich

Metabolic rewiring tunes dermal macrophages in staphylococcal skin infection.
Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis.
The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials.
The respiratory microbiota and its impact on health and disease in dogs and cats: A One Health perspective.
The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease.
Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease.
The Dual Role of ACOD1 in Inflammation.
Fc receptors act as innate immune receptors during infection?
Lipopolysaccharide Tolerance in Human Primary Monocytes and Polarized Macrophages.
Programmed Necrosis in Host Defense.
Remembering foods and foes: emerging principles of transcriptional memory.
Epithelial inflammasomes, gasdermins, and mucosal inflammation - Lessons from Salmonella and Shigella infected mice.
Early Life Exposure to Human Milk Oligosaccharides Reduces Allergic Response in a Murine Asthma Model.
Bacterial amylases enable glycogen degradation by the vaginal microbiome.
Human Macrophages Polarized by Interaction with Apoptotic Cells Produce Fibrosis-Associated Mediators and Enhance Pro-Fibrotic Activity of Dermal Fibroblasts In Vitro.
Mechanisms and Effects of Macrophage Polarization and Its Specifics in Pulmonary Environment.
The role of the antigen processing machinery in the regulation and trafficking of intracellular -Toll-like receptor molecules.
Apoptotic bodies inhibit inflammation by PDL1-PD1-mediated macrophage metabolic reprogramming.
Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity.
Bacterial community analysis identifies Klebsiella pneumoniae as a native symbiotic bacterium in the newborn Protobothrops mucrosquamatus.
Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis.
Exploring Influenza A Virus-Induced Lung Injury and Immune Response Based on Humanized Lung-on-Chip.
Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community.
Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death.
The role of DNA methylation in personalized medicine for immune-related diseases.
Targeting Epithelium Dysfunction and Impaired Nasal Biofilms to Treat Immunological, Functional, and Structural Abnormalities of Chronic Rhinosinusitis.
Guanylate-binding proteins: mechanisms of pattern recognition and antimicrobial functions.
Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.
TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity.
Intestinal Immune Imbalance is an Alarm in the Development of IBD.
Targeting Th17 cells: a promising strategy to treat oral mucosal inflammatory diseases.
The Lung Microbiome in COPD and Lung Cancer: Exploring the Potential of Metal-Based Drugs.

Sci Immunol. 2023 Aug 18. 8(86): eadg3517

Metabolic rewiring tunes dermal macrophages in staphylococcal skin infection.

Aaron James Forde, Julia Kolter, Pascale Zwicky, Sebastian Baasch, Florens Lohrmann, Marleen Eckert, Vitka Gres, Simon Lagies, Oliver Gorka, Angelika S Rambold, Joerg M Buescher, Bernd Kammerer, Nico Lachmann, Marco Prinz, Olaf Groß, Edward J Pearce, Burkhard Becher, Philipp Henneke.

The skin needs to balance tolerance of colonizing microflora with rapid detection of potential pathogens. Flexible response mechanisms would seem most suitable to accommodate the dynamic challenges of effective antimicrobial defense and restoration of tissue homeostasis. Here, we dissected macrophage-intrinsic mechanisms and microenvironmental cues that tune macrophage signaling in localized skin infection with the colonizing and opportunistic pathogen Staphylococcus aureus. Early in skin infection, the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) produced by γδ T cells and hypoxic conditions within the dermal microenvironment diverted macrophages away from a homeostatic M-CSF- and hypoxia-inducible factor 1α (HIF-1α)-dependent program. This allowed macrophages to be metabolically rewired for maximal inflammatory activity, which requires expression of Irg1 and generation of itaconate, but not HIF-1α. This multifactorial macrophage rewiring program was required for both the timely clearance of bacteria and for the provision of local immune memory. These findings indicate that immunometabolic conditioning allows dermal macrophages to cycle between antimicrobial activity and protection against secondary infections.

DOI: https://doi.org/10.1126/sciimmunol.adg3517
bioRxiv. 2023 Jul 25. pii: 2023.07.21.550012. [Epub ahead of print]

Microbial community organization designates distinct pulmonary exacerbation types and predicts treatment outcome in cystic fibrosis.

Stefanie Widder, Kristopher Opron, Lisa A Carmody, Linda M Kalikin, Lindsay J Caverly, John J LiPuma.

Polymicrobial infection of the airways is a hallmark of obstructive lung diseases such as cystic fibrosis (CF), non-CF bronchiectasis, and chronic obstructive pulmonary disease (COPD). Intermittent pulmonary exacerbations (PEx) in these conditions are associated with lung function decline and higher mortality rates. An understanding of the microbial underpinnings of PEx is challenged by high inter-patient variability in airway microbial community profiles. We analyzed 880 near-daily CF sputum samples and developed non-standard microbiome descriptors to model community reorganization prior and during 18 PEx. We identified two communal microbial regimes with opposing ecology and dynamics. Whereas pathogen-governed dysbiosis showed hierarchical community organization and reduced diversity, anaerobic bloom dysbiosis displayed stochasticity and increased diversity. Microbiome organization modulated the relevance of pathogens and a simulation of antimicrobial treatment predicted better efficacy for hierarchically organized microbiota. This causal link between PEx, microbiome organization, and treatment success advances the development of personalized dysbiosis management in CF and, potentially, other obstructive lung diseases.

DOI: https://doi.org/10.1101/2023.07.21.550012
Biomed Pharmacother. 2023 Aug 03. pii: S0753-3322(23)01067-3. [Epub ahead of print]165 115276

The impact of microbiota-derived short-chain fatty acids on macrophage activities in disease: Mechanisms and therapeutic potentials.

Hongliang Duan, LiJuan Wang, Mingmei Huangfu, Hanyang Li.

  Short-chain fatty acids (SCFAs) derived from the fermentation of carbohydrates by gut microbiota play a crucial role in regulating host physiology. Among them, acetate, propionate, and butyrate are key players in various biological processes. Recent research has revealed their significant functions in immune and inflammatory responses. For instance, butyrate reduces the development of interferon-gamma (IFN-γ) generating cells while promoting the development of regulatory T (Treg) cells. Propionate inhibits the initiation of a Th2 immune response by dendritic cells (DCs). Notably, SCFAs have an inhibitory impact on the polarization of M2 macrophages, emphasizing their immunomodulatory properties and potential for therapeutics. In animal models of asthma, both butyrate and propionate suppress the M2 polarization pathway, thus reducing allergic airway inflammation. Moreover, dysbiosis of gut microbiota leading to altered SCFA production has been implicated in prostate cancer progression. SCFAs trigger autophagy in cancer cells and promote M2 polarization in macrophages, accelerating tumor advancement. Manipulating microbiota- producing SCFAs holds promise for cancer treatment. Additionally, SCFAs enhance the expression of hypoxia-inducible factor 1 (HIF-1) by blocking histone deacetylase, resulting in increased production of antibacterial effectors and improved macrophage-mediated elimination of microorganisms. This highlights the antimicrobial potential of SCFAs and their role in host defense mechanisms. This comprehensive review provides an in-depth analysis of the latest research on the functional aspects and underlying mechanisms of SCFAs in relation to macrophage activities in a wide range of diseases, including infectious diseases and cancers. By elucidating the intricate interplay between SCFAs and macrophage functions, this review aims to contribute to the understanding of their therapeutic potential and pave the way for future interventions targeting SCFAs in disease management.

Keywords:  Autoimmunity; Cancer; Infection; M2 polarization; Macrophage; Short-chain fatty acids

DOI:  https://doi.org/10.1016/j.biopha.2023.115276
J Vet Intern Med. 2023 Aug 08.

The respiratory microbiota and its impact on health and disease in dogs and cats: A One Health perspective.

Aida I Vientós-Plotts, Aaron C Ericsson, Carol R Reinero.

  Healthy lungs were long thought of as sterile, with presence of bacteria identified by culture representing contamination. Recent advances in metagenomics have refuted this belief by detecting rich, diverse, and complex microbial communities in the healthy lower airways of many species, albeit at low concentrations. Although research has only begun to investigate causality and potential mechanisms, alterations in these microbial communities (known as dysbiosis) have been described in association with inflammatory, infectious, and neoplastic respiratory diseases in humans. Similar studies in dogs and cats are scarce. The microbial communities in the respiratory tract are linked to distant microbial communities such as in the gut (ie, the gut-lung axis), allowing interplay of microbes and microbial products in health and disease. This review summarizes considerations for studying local microbial communities, key features of the respiratory microbiota and its role in the gut-lung axis, current understanding of the healthy respiratory microbiota, and examples of dysbiosis in selected respiratory diseases of dogs and cats.

Keywords:  asthma; lung; microbiome; nasal; pneumonia

DOI:  https://doi.org/10.1111/jvim.16824
Cells. 2023 Jul 31. pii: 1981. [Epub ahead of print]12(15):

The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease.

Maria Tsioumpekou, Daniëlle Krijgsman, Jeanette H W Leusen, Patricia A Olofsen.

  Neutrophils are crucial innate immune cells and comprise 50-70% of the white blood cell population under homeostatic conditions. Upon infection and in cancer, blood neutrophil numbers significantly increase because of the secretion of various chemo- and cytokines by, e.g., leukocytes, pericytes, fibroblasts and endothelial cells present in the inflamed tissue or in the tumor microenvironment (TME). The function of neutrophils in cancer has recently gained considerable attention, as they can exert both pro- and anti-tumorigenic functions, dependent on the cytokine milieu present in the TME. Here, we review the effect of cytokines on neutrophil development, tissue homing, function and plasticity in cancer and autoimmune diseases as well as under physiological conditions in the bone marrow, bloodstream and various organs like the spleen, kidney, liver, lung and lymph nodes. In addition, we address several promising therapeutic options, such as cytokine therapy, immunocytokines and immunotherapy, which aim to exploit the anti-tumorigenic potential of neutrophils in cancer treatment or block excessive neutrophil-mediated inflammation in autoimmune diseases.

Keywords:  NETs; TME; autoimmune diseases; cancer; cytokine therapeutics; cytokines; immunocytokines; immunotherapy; neutrophils; tissue-resident neutrophils; tumor microenvironment

DOI:  https://doi.org/10.3390/cells12151981
Discov Immunol. 2023 ;2(1): kyad009

Comparative phenotype of circulating versus tissue immune cells in human lung and blood compartments during health and disease.

Stefano A P Colombo, Sheila L Brown, Matthew R Hepworth, Jenny Hankinson, Felice Granato, Semra J Kitchen, Tracy Hussell, Angela Simpson, Peter C Cook, Andrew S MacDonald.

  The lung is a dynamic mucosal surface constantly exposed to a variety of immunological challenges including harmless environmental antigens, pollutants, and potentially invasive microorganisms. Dysregulation of the immune system at this crucial site is associated with a range of chronic inflammatory conditions including asthma and Chronic Pulmonary Obstructive Disease (COPD). However, due to its relative inaccessibility, our fundamental understanding of the human lung immune compartment is limited. To address this, we performed flow cytometric immune phenotyping of human lung tissue and matched blood samples that were isolated from 115 donors undergoing lung tissue resection. We provide detailed characterization of the lung mononuclear phagocyte and T cell compartments, demonstrating clear phenotypic differences between lung tissue cells and those in peripheral circulation. Additionally, we show that CD103 expression demarcates pulmonary T cells that have undergone recent TCR and IL-7R signalling. Unexpectedly, we discovered that the immune landscape from asthmatic or COPD donors was broadly comparable to controls. Our data provide a much-needed expansion of our understanding of the pulmonary immune compartment in both health and disease.

Keywords:  COPD; T cells; asthma; dendritic cells; mucosal immunology

DOI:  https://doi.org/10.1093/discim/kyad009
J Immunol. 2023 08 15. 211(4): 518-526

The Dual Role of ACOD1 in Inflammation.

Runliu Wu, Jiao Liu, Daolin Tang, Rui Kang.

Immunometabolism is an interdisciplinary field that focuses on the relationship between metabolic pathways and immune responses. Dysregulated immunometabolism contributes to many pathological settings, such as cytokine storm or immune tolerance. Aconitate decarboxylase 1 (ACOD1, also known as immunoresponsive gene 1), the mitochondrial enzyme responsible for catalyzing itaconate production, was originally identified as a bacterial LPS-inducible gene involved in innate immunity in mouse macrophages. We now know that the upregulation of ACOD1 expression in immune or nonimmune cells plays a context-dependent role in metabolic reprogramming, signal transduction, inflammasome regulation, and protein modification. The emerging function of ACOD1 in inflammation and infection is a double-edged sword. In this review, we discuss how ACOD1 regulates anti-inflammatory or proinflammatory responses in an itaconate-dependent or -independent manner. Further understanding of ACOD1 expression and function may pave the way for the development of precision therapies for inflammatory diseases.

DOI: https://doi.org/10.4049/jimmunol.2300101
Front Immunol. 2023 ;14 1188497

Fc receptors act as innate immune receptors during infection?

Chaimaa Laassili, Fatiha Ben El Hend, Riad Benzidane, Loubna Oumeslakht, Abdel-Ilah Aziz, Rachid El Fatimy, Armand Bensussan, Sanae Ben Mkaddem.

  Innate immunity constitutes the first nonspecific immunological line of defense against infection. In this response, a variety of mechanisms are activated: the complement system, phagocytosis, and the inflammatory response. Then, adaptive immunity is activated. Major opsonization mediators during infections are immunoglobulins (Igs), the function of which is mediated through Fc receptors (FcRs). However, in addition to their role in adaptive immunity, FcRs have been shown to play a role in innate immunity by interacting directly with bacteria in the absence of their natural ligands (Igs). Additionally, it has been hypothesized that during the early phase of bacterial infection, FcRs play a protective role via innate immune functions mediated through direct recognition of bacteria, and as the infection progresses to later phases, FcRs exhibit their established function as receptors in adaptive immunity. This review provides detailed insight into the potential role of FcRs as innate immune mediators of the host defense against bacterial infection independent of opsonins.

Keywords:  FcR; ITAM bearing receptors; bacterial clearance; infection; innate immunity

DOI:  https://doi.org/10.3389/fimmu.2023.1188497
Int J Mol Sci. 2023 Jul 30. pii: 12196. [Epub ahead of print]24(15):

Lipopolysaccharide Tolerance in Human Primary Monocytes and Polarized Macrophages.

Hui Li, Annette Breedijk, Nadine Dietrich, Katja Nitschke, Jonas Jarczyk, Philipp Nuhn, Bernhard K Krämer, Benito A Yard, Jan Leipe, Sibylle Hauske.

  Innate immune memory allows macrophages to adequately respond to pathogens to which they have been pre-exposed. To what extent different pattern recognition receptors, cytokines and resolution signals influence innate immune memory needs further elucidation. The present study assessed whether lipopolysaccharide (LPS) tolerance in monocytes and macrophages is affected by these factors. Human CD14+ cells were isolated from peripheral blood, stimulated by LPS and re-stimulated after 3 days of resting. Hereafter, immune-responsive gene 1 (IRG-1), heme oxygenase 1 (HO-1), tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) expression were assessed. Our study revealed the following findings: (1) While pre-stimulation with the Toll-like receptor 4 ligand LPS inhibits the induction of IRG-1, TNF-α and IL-6 expression, pre-stimulation with TLR 1/2 ligands only affects cytokine production but not IRG-1 expression upon subsequent TLR4 engagement. (2) Prior TNF-α stimulation does not affect LPS tolerance but rather increases LPS-mediated cytokine expression. (3) Dimethyl itaconate (DMI) inhibits the expression of IRG-1 in a dose-dependent manner but does not affect TNF-α or IL-6 expression. (4) Docosahexaenoic acid (DHA) partly inhibits IRG-1 expression in monocytes but not in M(IFNγ) and M(IL-4) polarized macrophages. LPS tolerance is not affected in these cells by DHA. The data presented in this study partly corroborate and extend previous findings on innate immune memory and warrant further studies on LPS tolerance to gain a better understanding of innate immune memory at the molecular level.

Keywords:  DHA; DMI; LPS tolerance; TLR agonists; innate immune memory; macrophages; monocytes; trained immunity

DOI:  https://doi.org/10.3390/ijms241512196
Curr Top Microbiol Immunol. 2023 Aug 11.

Programmed Necrosis in Host Defense.

Edward S Mocarski.

  Host control over infectious disease relies on the ability of cells in multicellular organisms to detect and defend against pathogens to prevent disease. Evolution affords mammals with a wide variety of independent immune mechanisms to control or eliminate invading infectious agents. Many pathogens acquire functions to deflect these immune mechanisms and promote infection. Following successful invasion of a host, cell autonomous signaling pathways drive the production of inflammatory cytokines, deployment of restriction factors and induction of cell death. Combined, these innate immune mechanisms attract dendritic cells, neutrophils and macrophages as well as innate lymphoid cells such as natural killer cells that all help control infection. Eventually, the development of adaptive pathogen-specific immunity clears infection and provides immune memory of the encounter. For obligate intracellular pathogens such as viruses, diverse cell death pathways make a pivotal contribution to early control by eliminating host cells before progeny are produced. Pro-apoptotic caspase-8 activity (along with caspase-10 in humans) executes extrinsic apoptosis, a nonlytic form of cell death triggered by TNF family death receptors (DRs). Over the past two decades, alternate extrinsic apoptosis and necroptosis outcomes have been described. Programmed necrosis, or necroptosis, occurs when receptor interacting protein kinase 3 (RIPK3) activates mixed lineage kinase-like (MLKL), causing cell leakage. Thus, activation of DRs, toll-like receptors (TLRs) or pathogen sensor Z-nucleic acid binding protein 1 (ZBP1) initiates apoptosis as well as necroptosis if not blocked by virus-encoded inhibitors. Mammalian cell death pathways are blocked by herpesvirus- and poxvirus-encoded cell death suppressors. Growing evidence has revealed the importance of Z-nucleic acid sensor, ZBP1, in the cell autonomous recognition of both DNA and RNA virus infection. This volume will explore the detente between viruses and cells to manage death machinery and avoid elimination to support dissemination within the host animal.

Keywords:  Apoptosis; Herpesvirus; Necroptosis; Poxvirus; Programed cell death; Z-nucleic acid binding protein

DOI:  https://doi.org/10.1007/82_2023_264
Cell Death Differ. 2023 Aug 10.

Remembering foods and foes: emerging principles of transcriptional memory.

Sahar S H Tehrani, Anna Kogan, Pawel Mikulski, Lars E T Jansen.

Transcriptional memory is characterized by a primed cellular state, induced by an external stimulus that results in an altered expression of primed genes upon re-exposure to the inducing signal. Intriguingly, the primed state is heritably maintained across somatic cell divisions even after the initial stimulus and target gene transcription cease. This phenomenon is widely observed across various organisms and appears to enable cells to retain a memory of external signals, thereby adapting to environmental changes. Signals range from nutrient supplies (food) to a variety of stress signals, including exposure to pathogens (foes), leading to long-term memory such as in the case of trained immunity in plants and mammals. Here, we review these priming phenomena and our current understanding of transcriptional memory. We consider different mechanistic models for how memory can work and discuss existing evidence for potential carriers of memory. Key molecular signatures include: the poising of RNA polymerase II machinery, maintenance of histone marks, as well as alterations in nuclear positioning and long-range chromatin interactions. Finally, we discuss the potential adaptive roles of transcriptional memory in the organismal response to its environment from nutrient sensing to trained immunity.

DOI: https://doi.org/10.1038/s41418-023-01200-6
Semin Immunol. 2023 Aug 08. pii: S1044-5323(23)00103-3. [Epub ahead of print]70 101812

Epithelial inflammasomes, gasdermins, and mucosal inflammation - Lessons from Salmonella and Shigella infected mice.

Ersin Gül, Stefan A Fattinger, Mikael E Sellin, Wolf-Dietrich Hardt.

  Besides its crucial function in nutrient absorbance and as barrier against the microbiota, the gut epithelium is essential for sensing pathogenic insults and mounting of an appropriate early immune response. In mice, the activation of the canonical NAIP/NLRC4 inflammasome is critical for the defense against enterobacterial infections. Activation of the NAIP/NLRC4 inflammasome triggers the extrusion of infected intestinal epithelial cells (IEC) into the gut lumen, concomitant with inflammasome-mediated lytic cell death. The membrane permeabilization, a hallmark of pyroptosis, is caused by the pore-forming proteins called gasdermins (GSDMs). Recent work has revealed that NAIP/NLRC4-dependent extrusion of infected IECs can, however, also be executed in the absence of GSDMD. In fact, several reports highlighted that various cell death pathways (e.g., pyroptosis or apoptosis) and unique mechanisms specific to particular infection models and stages of gut infection are in action during epithelial inflammasome defense against intestinal pathogens. Here, we summarize the current knowledge regarding the underlying mechanisms and speculate on the putative functions of the epithelial inflammasome activation and cell death, with a particular emphasis on mouse infection models for two prominent enterobacterial pathogens, Salmonella Typhimurium and Shigella flexneri.

Keywords:  Cell death; Epithelial cells; Gasdermins; Pyroptosis; Salmonella

DOI:  https://doi.org/10.1016/j.smim.2023.101812
J Immunol Res. 2023 ;2023 9603576

Early Life Exposure to Human Milk Oligosaccharides Reduces Allergic Response in a Murine Asthma Model.

Tahereh Bozorgmehr, Rozlyn C T Boutin, Sarah E Woodward, Katherine Donald, Jo May Chow, Rachael H Buck, B Brett Finlay.

Background: Studies suggest that early-life gut microbiota composition and intestinal short-chain fatty acids (SCFAs) are linked to future asthma susceptibility. Furthermore, infancy offers a critical time window to modulate the microbiota and associated metabolites through diet-microbe interactions to promote infant health. Human milk oligosaccharides (HMOs), nondigestible carbohydrates abundant in breast milk, are prebiotics selectively metabolized by gut microbiota that consequently modify microbiome composition and SCFA production.Methods: Using a house dust mite mouse model of allergy, we investigated the impacts of early oral treatment of pups with biologically relevant doses of 2'-fucosyllactose (2'-FL) and 6'-sialyllactose (6'-SL), two of the most abundant HMOs in human milk, in amelioration of allergic airway disease severity.
Results: We found that administration of 2'-FL and 6'-SL during early life reduced lung histopathology scores, circulating IgE, cytokine levels, and inflammatory cell infiltration, all hallmark symptoms of allergic asthma. HMO supplementation also increased the relative abundance of intestinal Bacteroidetes and Clostridia, known SCFA producers within the gut. Indeed, we detected increased SCFA concentrations in both the intestine and blood of adult mice who received HMOs prior to weaning.
Conclusion: We propose a model in which orally administered HMOs delivered during early life shift the microbiota toward increased production of SCFAs, which dampens the allergic immune responses behind allergy and asthma. Overall, these data suggest the potential for HMO supplementation to protect infants against asthma development later in life, with possible benefits against additional atopic diseases such as eczema and food allergies.

DOI: https://doi.org/10.1155/2023/9603576
Nat Microbiol. 2023 Aug 10.

Bacterial amylases enable glycogen degradation by the vaginal microbiome.

Dominick J Jenkins, Benjamin M Woolston, M Indriati Hood-Pishchany, Paula Pelayo, Alyssa N Konopaski, M Quinn Peters, Michael T France, Jacques Ravel, Caroline M Mitchell, Seth Rakoff-Nahoum, Christopher Whidbey, Emily P Balskus.

The human vaginal microbiota is frequently dominated by lactobacilli and transition to a more diverse community of anaerobic microbes is associated with health risks. Glycogen released by lysed epithelial cells is believed to be an important nutrient source in the vagina. However, the mechanism by which vaginal bacteria metabolize glycogen is unclear, with evidence implicating both bacterial and human enzymes. Here we biochemically characterize six glycogen-degrading enzymes (GDEs), all of which are pullanases (PulA homologues), from vaginal bacteria that support the growth of amylase-deficient Lactobacillus crispatus on glycogen. We reveal variations in their pH tolerance, substrate preferences, breakdown products and susceptibility to inhibition. Analysis of vaginal microbiome datasets shows that these enzymes are expressed in all community state types. Finally, we confirm the presence and activity of bacterial and human GDEs in cervicovaginal fluid. This work establishes that bacterial GDEs can participate in the breakdown of glycogen, providing insight into metabolism that may shape the vaginal microbiota.

DOI: https://doi.org/10.1038/s41564-023-01447-2
Cells. 2023 Jul 25. pii: 1928. [Epub ahead of print]12(15):

Human Macrophages Polarized by Interaction with Apoptotic Cells Produce Fibrosis-Associated Mediators and Enhance Pro-Fibrotic Activity of Dermal Fibroblasts In Vitro.

Aleksandra Maksimova, Ekaterina Shevela, Lyudmila Sakhno, Marina Tikhonova, Aleksandr Ostanin, Elena Chernykh.

  Apoptosis and subsequent removal of dead cells are an essential part of wound healing. Macrophages phagocytize apoptotic cells (efferocytosis) and contribute to the resolution of inflammation. However, their participation in fibrogenesis and the mechanisms of influence on this process remain unclear. In the present study, we focused on the fibrogenic properties of human monocyte-derived macrophages polarized in the M2 direction by interaction with apoptotic cells. We studied their influence on the proliferation ([3H]-thymidine incorporation), differentiation (by the expression of α-SMA, a myofibroblast marker) and collagen-producing activity (ELISA) of dermal fibroblasts compared to classically (LPS) and alternatively (IL-4) activated macrophages. Macrophages polarized by the interaction with apoptotic cells had a unique phenotype and profile of produced factors and differed from the compared macrophage subtypes. Their conditioned media promoted the proliferation of dermal fibroblasts and the expression of α-SMA in them at the level of macrophages stimulated by IL-4, while the stimulating effect on the collagen-producing activity was more pronounced compared to that of the other macrophage subtypes. Moreover, they are characterized by the high level of production of pro-fibrotic factors such as TIMP-1, TGF-β1 and angiogenin. Taken together, M2-like macrophages polarized by efferocytosis demonstrate in vitro pro-fibrotic activity by promoting the functional activity of dermal fibroblasts and producing pro-fibrotic and pro-angiogenic factors.

Keywords:  collagen; efferocytosis; fibroblast; macrophage; matrix metalloproteinase; repair; wound healing

DOI:  https://doi.org/10.3390/cells12151928
Physiol Res. 2023 Jul 31. 72(Suppl 2): S137-S156

Mechanisms and Effects of Macrophage Polarization and Its Specifics in Pulmonary Environment.

M Žaloudíková.

Macrophages are a specific group of cells found in all body tissues. They have specific characteristics in each of the tissues that correspond to the functional needs of the specific environment. These cells are involved in a wide range of processes, both pro-inflammatory and anti-inflammatory ("wound healing"). This is due to their specific capacity for so-called polarization, a phenotypic change that is, moreover, partially reversible compared to other differentiated cells of the human body. This promises a wide range of possibilities for its influence and thus therapeutic use. In this article, we therefore review the mechanisms that cause polarization, the basic classification of polarized macrophages, their characteristic markers and the effects that accompany these phenotypic changes. Since the study of pulmonary (and among them mainly alveolar) macrophages is currently the focus of scientific interest of many researchers and these macrophages are found in very specific environments, given mainly by the extremely high partial pressure of oxygen compared to other locations, which specifically affects their behavior, we will focus our review on this group.
Curr Opin Immunol. 2023 Aug 08. pii: S0952-7915(23)00094-8. [Epub ahead of print]84 102375

The role of the antigen processing machinery in the regulation and trafficking of intracellular -Toll-like receptor molecules.

Moïse de Lavergne, Lucie Maisonneuve, Katrina Podsypanina, Bénédicte Manoury.

Intracellular Toll-like receptors (TLRs) are key components of the innate immune system. Their expression in antigen-presenting cells (APCs), and in particular dendritic cells (DCs), makes them critical in the induction of the adaptive immune response. In DCs, they interact with the chaperone UNC93B1 that mediates their trafficking from the endoplasmic reticulum (ER) to endosomes where they are cleaved by proteases and activated. All these different steps are also shared by major histocompatibility complex class-II (MHCII) molecules. Here, we will discuss the tight relationship intracellular TLRs have with the antigen processing machinery in APCs for their trafficking and activation.

DOI: https://doi.org/10.1016/j.coi.2023.102375
Cell Prolif. 2023 Aug 08. e13531

Apoptotic bodies inhibit inflammation by PDL1-PD1-mediated macrophage metabolic reprogramming.

Tao Jiang, Yanmin Xia, Wenzhe Wang, Jinbo Zhao, Wenhao Liu, Shiyu Liu, Songtao Shi, Bei Li, Xiaoning He, Yan Jin.

Apoptosis triggers immunoregulation to prevent and suppress inflammation and autoimmunity. However, the mechanism by which apoptotic cells modulate immune responses remains largely elusive. In the context of allogeneic mesenchymal stem cells (MSCs) transplantation, long-term immunoregulation is observed in the host despite the short survive of the injected MSCs. In this study, utilizing a mouse model of acute lung injury (ALI), we demonstrate that apoptotic bodies (ABs) released by transplanted human umbilical cord MSCs (UC-MSCs) convert the macrophages from a pro-inflammatory to an anti-inflammatory state, thereby ameliorating the disease. Mechanistically, we identify the expression of programmed cell death 1 ligand 1 (PDL1) on the membrane of UC-MSCs-derived ABs, which interacts with programmed cell death protein 1 (PD1) on host macrophages. This interaction leads to the reprogramming of macrophage metabolism, shifting from glycolysis to mitochondrial oxidative phosphorylation via the Erk-dependent pathway in ALI. Importantly, we have reproduced the PDL1-PD1 effects of ABs on metabolic switch using alveolar macrophages from patients with ALI, suggesting the potential clinical implications of developing therapeutic strategies for the patients.

DOI: https://doi.org/10.1111/cpr.13531
Int J Mol Sci. 2023 Jul 27. pii: 12032. [Epub ahead of print]24(15):

Impact of Lipid Metabolism on Macrophage Polarization: Implications for Inflammation and Tumor Immunity.

Evros Vassiliou, Renalison Farias-Pereira.

  Macrophage polarization is influenced by lipids, which also exert significant control over macrophage functions. Lipids and their metabolites are players in intricate signaling pathways that modulate macrophages' responses to pathogens, phagocytosis, ferroptosis, and inflammation. This review focuses on lipid metabolism and macrophage functions and addresses potential molecular targets for the treatment of macrophage-related diseases. While lipogenesis is crucial for lipid accumulation and phagocytosis in M1 macrophages, M2 macrophages likely rely on fatty acid β-oxidation to utilize fatty acids as their primary energy source. Cholesterol metabolism, regulated by factors such as SREBPs, PPARs, and LXRs, is associated with the cholesterol efflux capacity and the formation of foam cells (M2-like macrophages). Foam cells, which are targets for atherosclerosis, are associated with an increase in inflammatory cytokines. Lipolysis and fatty acid uptake markers, such as CD36, also contribute to the production of cytokines. Enhancing the immune system through the inhibition of lipid-metabolism-related factors can potentially serve as a targeted approach against tumor cells. Cyclooxygenase inhibitors, which block the conversion of arachidonic acid into various inflammatory mediators, influence macrophage polarization and have generated attention in cancer research.

Keywords:  cancer; inflammation; lipid; macrophage; metabolism; polarization

DOI:  https://doi.org/10.3390/ijms241512032
BMC Microbiol. 2023 Aug 08. 23(1): 213

Bacterial community analysis identifies Klebsiella pneumoniae as a native symbiotic bacterium in the newborn Protobothrops mucrosquamatus.

Hung-Yuan Su, Bashir Hussain, Bing-Mu Hsu, Kuo-Hsin Lee, Yan-Chiao Mao, Liao-Chun Chiang, Jung-Sheng Chen.

BACKGROUND: The study of the native microbiome of organisms is crucial. The connection between the native microbiome and the host affects the formation of the innate immune system and the organism's growth. However, the native microbiome of newborn venomous snakes has not been reported. Therefore, we aimed to determine the oral and skin microbiomes of newborn Protobothrops mucrosquamatus.RESULTS: We performed 16 S full-length sequencing on 14 samples collected from 7 newborn P. mucrosquamatus individuals, specifically targeting their oral and skin microbiomes. In terms of the oral and skin microbiome, the main species were Klebsiella pneumoniae lineages. According to subspecies/species analysis, the proportion from highest to lowest was K. quasipneumoniae subsp. similipneumoniae, K. pneumoniae subsp. pneumoniae, and K. pneumoniae subsp. rhinoscleromatis. These three bacteria accounted for 62.5% and 85% of the skin and oral activity, respectively. The oral microbiome of newborn P. mucrosquamatus did not comprise common bacteria found in snakebite wounds or oral cultures in adult snakes. Therefore, the source of other microbiomes in the oral cavities of adult snakes may be the environment or prey. Functional Annotation of the Prokaryotic Taxa analysis showed that the skin/oral native microbiome metabolism was related to fermentation and human infection owing to the dominance of K. pneumoniae lineages. The characteristics of K. pneumoniae may impact the development of venom in venomous snakes.
CONCLUSION: The results of the native microbiome in the oral cavity and skin of newborn P. mucrosquamatus demonstrated that the habitat environment and prey capture may affect the composition of bacteria in adult snakes. We hypothesized that the native microbiome influences newborn venomous snakes and that K. pneumoniae lineages related to citrate fermentation may play a role in venom growth. However, further verification of this is required.

DOI: https://doi.org/10.1186/s12866-023-02936-4
Allergy. 2023 Aug 12.

Epigenetic responses to rhinovirus exposure in airway epithelial cells are correlated with key transcriptional pathways in chronic rhinosinusitis.

Marcus M Soliai, Atsushi Kato, Katherine A Naughton, James E Norton, Aiko I Klinger, Robert C Kern, Bruce K Tan, Dan L Nicolae, Robert P Schleimer, Carole Ober, Jayant M Pinto.

  BACKGROUND: Viruses may drive immune mechanisms responsible for chronic rhinosinusitis with nasal polyposis (CRSwNP), but little is known about the underlying molecular mechanisms.OBJECTIVES: To identify epigenetic and transcriptional responses to a common upper respiratory pathogen, rhinovirus (RV), that are specific to patients with CRSwNP using a primary sinonasal epithelial cell culture model.
METHODS: Airway epithelial cells were collected at surgery from patients with CRSwNP (cases) and from controls without sinus disease, cultured, and then exposed to RV or vehicle for 48 h. Differential gene expression and DNA methylation (DNAm) between cases and controls in response to RV were determined using linear mixed models. Weighted gene co-expression analysis (WGCNA) was used to identify (a) co-regulated gene expression and DNAm signatures, and (b) genes, pathways, and regulatory mechanisms specific to CRSwNP.
RESULTS: We identified 5585 differential transcriptional and 261 DNAm responses (FDR <0.10) to RV between CRSwNP cases and controls. These differential responses formed three co-expression/co-methylation modules that were related to CRSwNP and three that were related to RV (Bonferroni corrected p < .01). Most (95%) of the differentially methylated CpGs (DMCs) were in modules related to CRSwNP, whereas the differentially expressed genes (DEGs) were more equally distributed between the CRSwNP- and RV-related modules. Genes in the CRSwNP-related modules were enriched in known CRS and/or viral response immune pathways.
CONCLUSION: RV activates specific epigenetic programs and correlated transcriptional networks in the sinonasal epithelium of individuals with CRSwNP. These novel observations suggest epigenetic signatures specific to patients with CRSwNP modulate response to viral pathogens at the mucosal environmental interface. Determining how viral response pathways are involved in epithelial inflammation in CRSwNP could lead to therapeutic targets for this burdensome airway disorder.

Keywords:  DNA methylation; airway epithelium; chronic rhinosinusitis; gene expression; nasal polyposis

DOI:  https://doi.org/10.1111/all.15837
Discov Med. 2023 Aug;35(177): 539-552

Exploring Influenza A Virus-Induced Lung Injury and Immune Response Based on Humanized Lung-on-Chip.

Shaoyan Gu, Pan Pan, Jiang Wang, Yinghan Shi, Feng Shi, Yuhan Zhang, Wei Guan, Yan Cao, Haimao Qin, Qingzhong Wang, Lixin Xie.

  BACKGROUND: Influenza is an important respiratory tract pathogen that causes substantial seasonal and pandemic morbidity and mortality. The aim of this study was to systematically analyze the transcriptome characteristics of peripheral blood mononuclear cells (PBMCs) after influenza A virus infection by constructing a human lung microarray model composed of PBMCs to simulate the influenza A virus infection process.METHODS: A human lung microarray model was constructed using alveolar epithelial cells, vascular endothelial cells, alveolar macrophages and PBMCs, for simulation of the process of influenza A virus infection. The transcriptome characteristics of PBMCs after influenza A virus infection were analyzed by a single-cell RNA sequencing system.
RESULTS: The study could realistically mimic the structure and physiological functions of the alveoli in vitro using immunofluorescence staining and expression of the specific marker. After the influenza A virus infected the upper lung chip channels, the epithelial cells underwent a high inflammatory response and spread to endothelial cells. Under experimental conditions, the Influenza A virus infection did not compromise the integrity of epithelial cells, but caused damage to endothelial cells and barrier dysfunction. Single-cell RNA sequencing of PBMCs showed that B and cluster of differentiation 4 (CD4) T cells played important immunomodulatory roles in response to influenza A virus infection, including significantly activating type I interferon signaling pathway, regulating cytokine and chemokine signaling pathway. Especially genes involved in cellular communication were significantly highly expressed post-infection.
CONCLUSIONS: All these results suggested that the interactions among immune cells played a crucial role in endothelial cell injury and immune cell recruitment after influenza virus infection. This lung-on-chip infection model combined with single-cell RNA sequencing provided a unique platform that can closely investigate the lung immune response to influenza A virus infection and new therapeutic strategies for influenza.

Keywords:  epithelial/endothelial barrier; immune cells; influenza A virus; lung-on-chip; single-cell RNA sequencing

DOI:  https://doi.org/10.24976/Discov.Med.202335177.55
Nat Commun. 2023 08 08. 14(1): 4780

Nutritional and host environments determine community ecology and keystone species in a synthetic gut bacterial community.

Anna S Weiss, Lisa S Niedermeier, Alexandra von Strempel, Anna G Burrichter, Diana Ring, Chen Meng, Karin Kleigrewe, Chiara Lincetto, Johannes Hübner, Bärbel Stecher.

A challenging task to understand health and disease-related microbiome signatures is to move beyond descriptive community-level profiling towards disentangling microbial interaction networks. Using a synthetic gut bacterial community, we aimed to study the role of individual members in community assembly, identify putative keystone species and test their influence across different environments. Single-species dropout experiments reveal that bacterial strain relationships strongly vary not only in different regions of the murine gut, but also across several standard culture media. Mechanisms involved in environment-dependent keystone functions in vitro include exclusive access to polysaccharides as well as bacteriocin production. Further, Bacteroides caecimuris and Blautia coccoides are found to play keystone roles in gnotobiotic mice by impacting community composition, the metabolic landscape and inflammatory responses. In summary, the presented study highlights the strong interdependency between bacterial community ecology and the biotic and abiotic environment. These results question the concept of universally valid keystone species in the gastrointestinal ecosystem and underline the context-dependency of both, keystone functions and bacterial interaction networks.

DOI: https://doi.org/10.1038/s41467-023-40372-0
Nat Rev Mol Cell Biol. 2023 Aug 11.

Roles of RIPK1 as a stress sentinel coordinating cell survival and immunogenic cell death.

Jarama Clucas, Pascal Meier.

Cell death and inflammation are closely linked arms of the innate immune response to combat infection and tissue malfunction. Recent advancements in our understanding of the intricate signals originating from dying cells have revealed that cell death serves as more than just an end point. It facilitates the exchange of information between the dying cell and cells of the tissue microenvironment, particularly immune cells, alerting and recruiting them to the site of disturbance. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is emerging as a critical stress sentinel that functions as a molecular switch, governing cellular survival, inflammatory responses and immunogenic cell death signalling. Its tight regulation involves multiple layers of post-translational modifications. In this Review, we discuss the molecular mechanisms that regulate RIPK1 to maintain homeostasis and cellular survival in healthy cells, yet drive cell death in a context-dependent manner. We address how RIPK1 mutations or aberrant regulation is associated with inflammatory and autoimmune disorders and cancer. Moreover, we tease apart what is known about catalytic and non-catalytic roles of RIPK1 and discuss the successes and pitfalls of current strategies that aim to target RIPK1 in the clinic.

DOI: https://doi.org/10.1038/s41580-023-00623-w
Pharmacol Ther. 2023 Aug 09. pii: S0163-7258(23)00172-9. [Epub ahead of print] 108508

The role of DNA methylation in personalized medicine for immune-related diseases.

Manoj Kumar Gupta, He Peng, Yang Li, Cheng-Jian Xu.

  Epigenetics functions as a bridge between host genetic & environmental factors, aiding in human health and diseases. Many immune-related diseases, including infectious and allergic diseases, have been linked to epigenetic mechanisms, particularly DNA methylation. In this review, we summarized an updated overview of DNA methylation and its importance in personalized medicine, and demonstrated that DNA methylation has excellent potential for disease prevention, diagnosis, and treatment in a personalized manner. The future implications and limitations of the DNA methylation study have also been well-discussed.

Keywords:  DNA methylation; Epigenetics; Personalized medicine

DOI:  https://doi.org/10.1016/j.pharmthera.2023.108508
Int J Mol Sci. 2023 Aug 03. pii: 12379. [Epub ahead of print]24(15):

Targeting Epithelium Dysfunction and Impaired Nasal Biofilms to Treat Immunological, Functional, and Structural Abnormalities of Chronic Rhinosinusitis.

Konstantinos Petalas, John Goudakos, George N Konstantinou.

  Chronic rhinosinusitis (CRS) with (CRSwNP) or without (CRSsNP) nasal polyps is a prevalent and heterogeneous disorder existing as a spectrum of clinical conditions with complex underlying pathomechanisms. CRS comprises a broad syndrome characterized by multiple immunological features involving complex interactions between the genes, the microbiome, host- and microbiota-derived exosomes, the epithelial barrier, and environmental and micromilieu exposures. The main pathophysiological feature is an epithelial barrier disruption, accompanied by microbiome alterations and unpredictable and multifactorial immunologic overreactions. Extrinsic pathogens and irritants interact with multiple epithelial receptors, which show distinct expression patterns, activate numerous signaling pathways, and lead to diverse antipathogen responses. CRSsNP is mainly characterized by fibrosis and mild inflammation and is often associated with Th1 or Th17 immunological profiles. CRSwNP appears to be associated with moderate or severe type 2 (T2) or Th2 eosinophilic inflammation. The diagnosis is based on clinical, endoscopic, and imaging findings. Possible CRS biomarkers from the peripheral blood, nasal secretions, tissue biopsies, and nasally exhaled air are studied to subgroup different CRS endotypes. The primary goal of CRS management is to maintain clinical control by nasal douching with isotonic or hypertonic saline solutions, administration of nasal and systemic steroids, antibiotics, biologic agents, or, in persistent and more severe cases, appropriate surgical procedures.

Keywords:  biofilm; biomarkers; cystic fibrosis; eosinophilic; granulomatosis; immunodeficiencies; microbiome; mucociliary clearance; nitric oxide; polyps; primary ciliary dyskinesia; type 2 inflammation

DOI:  https://doi.org/10.3390/ijms241512379
Trends Biochem Sci. 2023 Aug 09. pii: S0968-0004(23)00165-2. [Epub ahead of print]

Guanylate-binding proteins: mechanisms of pattern recognition and antimicrobial functions.

Max Kirkby, Daniel Enosi Tuipulotu, Shouya Feng, Jordan Lo Pilato, Si Ming Man.

  Guanylate-binding proteins (GBPs) are a family of intracellular proteins which have diverse biological functions, including pathogen sensing and host defense against infectious disease. These proteins are expressed in response to interferon (IFN) stimulation and can localize and target intracellular microbes (e.g., bacteria and viruses) by protein trafficking and membrane binding. These properties contribute to the ability of GBPs to induce inflammasome activation, inflammation, and cell death, and to directly disrupt pathogen membranes. Recent biochemical studies have revealed that human GBP1, GBP2, and GBP3 can directly bind to the lipopolysaccharide (LPS) of Gram-negative bacteria. In this review we discuss emerging data highlighting the functional versatility of GBPs, with a focus on their molecular mechanisms of pattern recognition and antimicrobial activity.

Keywords:  danger-associated molecular pattern molecules (DAMPs); innate immunity; interferon; lipopolysaccharide (LPS); pathogen-associated molecular pattern molecules (PAMPs)

DOI:  https://doi.org/10.1016/j.tibs.2023.07.002
Acta Pharmacol Sin. 2023 Aug 07.

Regulation of toll-like receptor (TLR) signaling pathways in atherosclerosis: from mechanisms to targeted therapeutics.

Mei Jin, Jian Fang, Jiao-Jiao Wang, Xin Shao, Suo-Wen Xu, Pei-Qing Liu, Wen-Cai Ye, Zhi-Ping Liu.

  Atherosclerosis, one of the life-threatening cardiovascular diseases (CVDs), has been demonstrated to be a chronic inflammatory disease, and inflammatory and immune processes are involved in the origin and development of the disease. Toll-like receptors (TLRs), a class of pattern recognition receptors that trigger innate immune responses by identifying pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs), regulate numerous acute and chronic inflammatory diseases. Recent studies reveal that TLRs have a vital role in the occurrence and development of atherosclerosis, including the initiation of endothelial dysfunction, interaction of various immune cells, and activation of a number of other inflammatory pathways. We herein summarize some other inflammatory signaling pathways, protein molecules, and cellular responses associated with TLRs, such as NLRP3, Nrf2, PCSK9, autophagy, pyroptosis and necroptosis, which are also involved in the development of AS. Targeting TLRs and their regulated inflammatory events could be a promising new strategy for the treatment of atherosclerotic CVDs. Novel drugs that exert therapeutic effects on AS through TLRs and their related pathways are increasingly being developed. In this article, we comprehensively review the current knowledge of TLR signaling pathways in atherosclerosis and actively seek potential therapeutic strategies using TLRs as a breakthrough point in the prevention and therapy of atherosclerosis.

Keywords:  Toll-like receptors; atherosclerosis; cardiovascular diseases; endothelial dysfunction; immune cells; inflammatory pathways

DOI:  https://doi.org/10.1038/s41401-023-01123-5
Elife. 2023 Aug 11. pii: e85647. [Epub ahead of print]12

TLR7 activation at epithelial barriers promotes emergency myelopoiesis and lung anti-viral immunity.

William David Jackson, Chiara Giacomassi, Sophie Ward, Amber Owen, Tiago C Luis, Sarah Spear, Kevin J Woollard, Cecilia Johansson, Jessica Strid, Marina Botto.

  Monocytes are heterogeneous innate effector leukocytes generated in the bone marrow and released into circulation in a CCR2-dependent manner. During infection or inflammation myelopoiesis is modulated to rapidly meet demand for more effector cells. Danger signals from peripheral tissues can influence this process. Herein we demonstrate that repetitive TLR7 stimulation via the epithelial barriers drove a potent emergency bone marrow monocyte response in mice. This process was unique to TLR7 activation and occurred independently of the canonical CCR2 and CX3CR1 axes or prototypical cytokines. The monocytes egressing the bone marrow had an immature Ly6C-high profile and differentiated into vascular Ly6C-low monocytes and tissue macrophages in multiple organs. They displayed a blunted cytokine response to further TLR7 stimulation and reduced lung viral load after RSV and influenza virus infection. These data provide insights into the emergency myelopoiesis likely to occur in response to the encounter of single-stranded RNA viruses at barrier sites.

Keywords:  immunology; inflammation; viruses

DOI:  https://doi.org/10.7554/eLife.85647
Mediators Inflamm. 2023 ;2023 1073984

Intestinal Immune Imbalance is an Alarm in the Development of IBD.

Chunli Hu, Shengtao Liao, Lin Lv, Chuanfei Li, Zhechuan Mei.

Immune regulation plays a crucial role in human health and disease. Inflammatory bowel disease (IBD) is a chronic relapse bowel disease with an increasing incidence worldwide. Clinical treatments for IBD are limited and inefficient. However, the pathogenesis of immune-mediated IBD remains unclear. This review describes the activation of innate and adaptive immune functions by intestinal immune cells to regulate intestinal immune balance and maintain intestinal mucosal integrity. Changes in susceptible genes, autophagy, energy metabolism, and other factors interact in a complex manner with the immune system, eventually leading to intestinal immune imbalance and the onset of IBD. These events indicate that intestinal immune imbalance is an alarm for IBD development, further opening new possibilities for the unprecedented development of immunotherapy for IBD.

DOI: https://doi.org/10.1155/2023/1073984
Front Immunol. 2023 ;14 1236856

Targeting Th17 cells: a promising strategy to treat oral mucosal inflammatory diseases.

Ying Wang, Ningning Xue, Ziyuan Wang, Xin Zeng, Ning Ji, Qianming Chen.

  With the improved quality of life, oral health is under increased pressure. Numerous common oral mucosal diseases, such as oral lichen planus(OLP) and gingivitis, are related to the destruction of the oral immune barrier. The cytokines secreted by T-helper 17 (Th17) cells are essential for maintaining oral immune homeostasis and play essential roles in immune surveillance. When antigens stimulate the epithelium, Th17 cells expand, differentiate, and generate inflammatory factors to recruit other lymphocytes, such as neutrophils, to clear the infection, which helps to maintain the integrity of the epithelial barrier. In contrast, excessive Th17/IL-17 axis reactions may cause autoimmune damage. Therefore, an in-depth understanding of the role of Th17 cells in oral mucosa may provide prospects for treating oral mucosal diseases. We reviewed the role of Th17 cells in various oral and skin mucosal systemic diseases with oral characteristics, and based on the findings of these reports, we emphasize that Th17 cellular response may be a critical factor in inflammatory diseases of the oral mucosa. In addition, we should pay attention to the role and relationship of "pathogenic Th17" and "non-pathogenic Th17" in oral mucosal diseases. We hope to provide a reference for Th17 cells as a potential therapeutic target for treating oral mucosal inflammatory disorders in the future.

Keywords:  T helper cells; Th17; oral inflammatory diseases; oral mucosa; oral mucosal immunity; periodontitis

DOI:  https://doi.org/10.3389/fimmu.2023.1236856
Int J Mol Sci. 2023 Aug 01. pii: 12296. [Epub ahead of print]24(15):

The Lung Microbiome in COPD and Lung Cancer: Exploring the Potential of Metal-Based Drugs.

Megan O'Shaughnessy, Orla Sheils, Anne-Marie Baird.

  Chronic obstructive pulmonary disease (COPD) and lung cancer 17 are two of the most prevalent and debilitating respiratory diseases worldwide, both associated with high morbidity and mortality rates. As major global health concerns, they impose a substantial burden on patients, healthcare systems, and society at large. Despite their distinct aetiologies, lung cancer and COPD share common risk factors, clinical features, and pathological pathways, which have spurred increasing research interest in their co-occurrence. One area of particular interest is the role of the lung microbiome in the development and progression of these diseases, including the transition from COPD to lung cancer. Exploring novel therapeutic strategies, such as metal-based drugs, offers a potential avenue for targeting the microbiome in these diseases to improve patient outcomes. This review aims to provide an overview of the current understanding of the lung microbiome, with a particular emphasis on COPD and lung cancer, and to discuss the potential of metal-based drugs as a therapeutic strategy for these conditions, specifically concerning targeting the microbiome.

Keywords:  chronic obstructive pulmonary disease; lung cancer; lung microbiome; metal-based drugs; metal-phen complexes; phenanthroline

DOI:  https://doi.org/10.3390/ijms241512296