bims-bac4me 2023-05-07 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023–05–07
twenty papers selected by
Chun-Chi Chang, Universitäts Spital Zürich

Pathogenic role of the staphylococcal accessory gene regulator quorum sensing system in atopic dermatitis.
Peptidoglycan-induced modulation of metabolic and inflammatory responses.
Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils.
The generation, activation, and polarization of monocyte-derived macrophages in human malignancies.
The role of monocyte-derived macrophages in the lung: it's all about context.
Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease.
Elevated expression of macrophage MERTK exhibits profibrotic effects and results in defective regulation of efferocytosis function in pulmonary fibrosis.
Diet, commensal microbiota-derived extracellular vesicles, and host immunity.
A mammalian lung's immune system minimizes tissue damage by initiating five major sequential phases of defense.
The gut microbiome: A line of defense against tuberculosis development.
Energy saver: Monocytes hibernate in bone marrow upon fasting.
Post-immunobiotics increase resistance to primary respiratory syncytial virus infection and secondary pneumococcal pneumonia.
The influence of high glucose conditions on macrophages and its effect on the autophagy pathway.
Host-pathogen biology intertwines in recurrent UTI.
Ultraviolet exposure regulates skin metabolome based on the microbiome.
An insight into the combination of probiotics and their implications for human health.
Metabolic pathways that permit Mycobacterium avium subsp. hominissuis to transition to different environments encountered within the host during infection.
Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases.
A new mouse model to study the early-life microbiome.
The Role of Diet and Gut Microbiota Interactions in Metabolic Homeostasis.

Front Cell Infect Microbiol. 2023 ;13 1178650

Pathogenic role of the staphylococcal accessory gene regulator quorum sensing system in atopic dermatitis.

Masakazu Tamai, Yuriko Yamazaki, Tomoka Ito, Seitaro Nakagawa, Yuumi Nakamura.

  The skin is home to various bacteria, archaea, fungi, and viruses, collectively referred to as the skin microbiota. Patients with certain skin diseases reportedly have unique skin "dysbiosis," a condition involving imbalanced microbiota, suggesting that dysbiosis in the skin may be either causal or a consequence of specific skin diseases. Atopic dermatitis (AD) is the most common allergic skin disease that affects 15-20% of children and 2-10% of adults worldwide. Both intrinsic genetic factors, such as susceptibility to type 2 inflammation or skin barrier dysfunction, and extrinsic environmental factors, such as air pollen and skin microbiota, contribute to AD. Staphylococcus aureus, which does not often colonize the skin of healthy individuals, is commonly identified in the lesional skin of patients with AD and is correlated with the disease flare. However, the role of S. aureus in the pathogenesis of AD has not been elucidated. Here, we discuss the pathological behavior of S. aureus, focusing on accessory gene regulator (Agr) quorum sensing, which is a fundamental bacterial cell-to-cell interaction mechanism that affects the behavior of S. aureus and other members of the microbial community. Importantly, beyond bacteria-bacteria interactions, the Agr quorum sensing system also regulates various virulence factors, which induce type 2 and IL-17-dependent skin inflammation in the host. Furthermore, the colonization of Agr-positive S. aureus in early life accelerates the development of pediatric AD. Finally, we aim to highlight the current efforts to establish novel therapeutic methods to ameliorate or prevent AD through Agr-targeted intervention.

Keywords:  Agr; IL-17; Staphycoccus aureus; Th2; atopic dermatits; dysbiosis; quorum sensing

DOI:  https://doi.org/10.3389/fcimb.2023.1178650
Immunometabolism (Cobham). 2023 Apr;5(2): e00024

Peptidoglycan-induced modulation of metabolic and inflammatory responses.

Andrea J Wolf.

  Bacterial cell wall peptidoglycan is composed of innate immune ligands and, due to its important structural role, also regulates access to many other innate immune ligands contained within the bacteria. There is a growing body of literature demonstrating how innate immune recognition impacts the metabolic functions of immune cells and how metabolic changes are not only important to inflammatory responses but are often essential. Peptidoglycan is primarily sensed in the context of the whole bacteria during lysosomal degradation; consequently, the innate immune receptors for peptidoglycan are primarily intracellular cytosolic innate immune sensors. However, during bacterial growth, peptidoglycan fragments are shed and can be found in the bloodstream of humans and mice, not only during infection but also derived from the abundant bacterial component of the gut microbiota. These peptidoglycan fragments influence cells throughout the body and are important for regulating inflammation and whole-body metabolic function. Therefore, it is important to understand how peptidoglycan-induced signals in innate immune cells and cells throughout the body interact to regulate how the body responds to both pathogenic and nonpathogenic bacteria. This mini-review will highlight key research regarding how cellular metabolism shifts in response to peptidoglycan and how systemic peptidoglycan sensing impacts whole-body metabolic function.

Keywords:  MDP; NOD1; NOD2; inflammation; metabolism; peptidoglycan

DOI:  https://doi.org/10.1097/IN9.0000000000000024
Annu Rev Immunol. 2023 04 26. 41 375-404

Origin and Heterogeneity of Tissue Myeloid Cells: A Focus on GMP-Derived Monocytes and Neutrophils.

Lai Guan Ng, Zhaoyuan Liu, Immanuel Kwok, Florent Ginhoux.

  Myeloid cells are a significant proportion of leukocytes within tissues, comprising granulocytes, monocytes, dendritic cells, and macrophages. With the identification of various myeloid cells that perform separate but complementary functions during homeostasis and disease, our understanding of tissue myeloid cells has evolved significantly. Exciting findings from transcriptomics profiling and fate-mapping mouse models have facilitated the identification of their developmental origins, maturation, and tissue-specific specializations. This review highlights the current understanding of tissue myeloid cells and the contributing factors of functional heterogeneity to better comprehend the complex and dynamic immune interactions within the healthy or inflamed tissue. Specifically, we discuss the new understanding of the contributions of granulocyte-monocyte progenitor-derived phagocytes to tissue myeloid cell heterogeneity as well as the impact of niche-specific factors on monocyte and neutrophil phenotype and function. Lastly, we explore the developing paradigm of myeloid cell heterogeneity during inflammation and disease.

Keywords:  GMP; fate-mapping; granulocyte-monocyte progenitors; macrophages; monocytes; neutrophils; niche; tissue reprogramming

DOI:  https://doi.org/10.1146/annurev-immunol-081022-113627
Front Immunol. 2023 ;14 1178337

The generation, activation, and polarization of monocyte-derived macrophages in human malignancies.

Paul Chaintreuil, Emeline Kerreneur, Maxence Bourgoin, Coline Savy, Cécile Favreau, Guillaume Robert, Arnaud Jacquel, Patrick Auberger.

  Macrophages are immune cells that originate from embryogenesis or from the differentiation of monocytes. They can adopt numerous phenotypes depending on their origin, tissue distribution and in response to different stimuli and tissue environment. Thus, in vivo, macrophages are endowed with a continuum of phenotypes that are rarely strictly pro-inflammatory or anti-inflammatory and exhibit a broad expression profile that sweeps over the whole polarization spectrum. Schematically, three main macrophage subpopulations coexist in human tissues: naïve macrophages also called M0, pro-inflammatory macrophages referred as M1 macrophages, and anti-inflammatory macrophages also known as M2 macrophages. Naïve macrophages display phagocytic functions, recognize pathogenic agents, and rapidly undergo polarization towards pro or anti-inflammatory macrophages to acquire their full panel of functions. Pro-inflammatory macrophages are widely involved in inflammatory response, during which they exert anti-microbial and anti-tumoral functions. By contrast, anti-inflammatory macrophages are implicated in the resolution of inflammation, the phagocytosis of cell debris and tissue reparation following injuries. Macrophages also play important deleterious or beneficial roles in the initiation and progression of different pathophysiological settings including solid and hematopoietic cancers. A better understanding of the molecular mechanisms involved in the generation, activation and polarization of macrophages is a prerequisite for the development of new therapeutic strategies to modulate macrophages functions in pathological situations.

Keywords:  CSF-1; LAM; TAM; differentiation; monocyte-derived macrophages; polarization; targeting macrophages

DOI:  https://doi.org/10.3389/fimmu.2023.1178337
Int J Biochem Cell Biol. 2023 Apr 29. pii: S1357-2725(23)00060-2. [Epub ahead of print] 106421

The role of monocyte-derived macrophages in the lung: it's all about context.

Wouter T'Jonck, Calum C Bain.

Macrophages are present in every tissue of the body where they play crucial roles in maintaining tissue homeostasis and providing front line defence against pathogens. Arguably, this is most important at mucosal barrier tissues, such as the lung and gut, which are major ports of entry for pathogens. However, a common feature of inflammation, infection or injury is the loss of tissue resident macrophages and accumulation of monocytes from the circulation, which differentiate, to different extents, into macrophages. The exact fate and function of these elicited, monocyte-derived macrophages in infection, injury and inflammation remains contentious. While some studies have documented the indispensable nature of monocytes and their macrophage derivatives in combatting infection and restoration of lung homeostasis following insult, observations from clinical studies and preclinical models of lung infection/injury shows that monocytes and their progeny can become dysregulated in severe pathology, often perpetuating rather than resolving the insult. In this Mini Review, we aim to bring together these somewhat contradictory reports by discussing how the plasticity of monocytes allow them to assume distinct functions in different contexts in the lung, from health to infection, and effective tissue repair to fibrotic disease.

DOI: https://doi.org/10.1016/j.biocel.2023.106421
Nat Rev Immunol. 2023 May 03.

Early-life interactions between the microbiota and immune system: impact on immune system development and atopic disease.

Katherine Donald, B Brett Finlay.

Prenatal and early postnatal life represent key periods of immune system development. In addition to genetics and host biology, environment has a large and irreversible role in the immune maturation and health of an infant. One key player in this process is the gut microbiota, a diverse community of microorganisms that colonizes the human intestine. The diet, environment and medical interventions experienced by an infant determine the establishment and progression of the intestinal microbiota, which interacts with and trains the developing immune system. Several chronic immune-mediated diseases have been linked to an altered gut microbiota during early infancy. The recent rise in allergic disease incidence has been explained by the 'hygiene hypothesis', which states that societal changes in developed countries have led to reduced early-life microbial exposures, negatively impacting immunity. Although human cohort studies across the globe have established a correlation between early-life microbiota composition and atopy, mechanistic links and specific host-microorganism interactions are still being uncovered. Here, we detail the progression of immune system and microbiota maturation in early life, highlight the mechanistic links between microbes and the immune system, and summarize the role of early-life host-microorganism interactions in allergic disease development.

DOI: https://doi.org/10.1038/s41577-023-00874-w
Respir Res. 2023 Apr 29. 24(1): 118

Elevated expression of macrophage MERTK exhibits profibrotic effects and results in defective regulation of efferocytosis function in pulmonary fibrosis.

Yixin She, Xin Xu, Qingyang Yu, Xiangsheng Yang, Jianxing He, Xiao Xiao Tang.

Increased apoptosis of alveolar epithelial cells is a prominent feature of pulmonary fibrosis. Macrophage efferocytosis, phagocytosis of apoptotic cells by macrophages, is crucial for maintaining tissue homeostasis. Expression of Mer tyrosine kinase (MERTK, an important recognition receptor in efferocytosis) in macrophages is thought to be associated with fibrosis. However, how macrophage MERTK affects pulmonary fibrosis and whether it depends on efferocytosis are not yet clear. Here, we found elevated MERTK expression in lung macrophages from IPF patients and mice with bleomycin-induced pulmonary fibrosis. In vitro experiments showed that macrophages overexpressing MERTK exhibit profibrotic effects and that macrophage efferocytosis abrogates the profibrotic effect of MERTK by downregulating MERTK, forming a negative regulatory loop. In pulmonary fibrosis, this negative regulation is defective, and MERTK mainly exhibits profibrotic effects. Our study reveals a previously unsuspected profibrotic effect of elevated macrophage MERTK in pulmonary fibrosis and defective regulation of efferocytosis function as a result of that elevation, suggesting that targeting MERTK in macrophages may help to attenuate pulmonary fibrosis.

DOI: https://doi.org/10.1186/s12931-023-02424-3
Eur J Immunol. 2023 May 03. e2250163

Diet, commensal microbiota-derived extracellular vesicles, and host immunity.

Jemma J Taitz, Jian K Tan, Camille Potier-Villette, Duan Ni, Nicholas Jc King, Ralph Nanan, Laurence Macia.

  The gut microbiota has co-evolved with its host, and commensal bacteria can influence both the host's immune development and function. Recently, a role has emerged for bacterial extracellular vesicles (BEVs) as potent immune modulators. BEVs are nanosized membrane vesicles produced by all bacteria, possessing membrane characteristic of the originating bacterium, and carrying an internal cargo that may include nucleic acid, proteins, and lipids and metabolites. Thus, BEVs possess multiple avenues for regulating immune processes, and have been implicated in allergic, autoimmune and metabolic diseases. BEVs are biodistributed locally in the gut, and also systemically, and thus have the potential to affect both the local and systemic immune response. The production of gut microbiota-derived BEVs are regulated by host factors, such as diet and antibiotic usage. Specifically, all aspects of nutrition including macronutrients (protein, carbohydrate and fat), micronutrients (Vitamins, minerals) and food additives (such as the antimicrobial sodium benzoate) can regulate BEV production. This review summarises current knowledge of the powerful links between nutrition, antibiotics, gut microbiota-derived BEV, and their effects on immunity and disease development. It highlights the potential of targeting or utilizing gut microbiota-derived BEV as a therapeutic intervention. This article is protected by copyright. All rights reserved.

Keywords:  diet; extracellular vesicles; gut microbiota; host-microbial physiology; immunity

DOI:  https://doi.org/10.1002/eji.202250163
Clin Exp Med. 2023 May 04.

A mammalian lung's immune system minimizes tissue damage by initiating five major sequential phases of defense.

Kevin Roe.

  The mammalian lungs encounter several pathogens, but have a sophisticated multi-phase immune defense. Furthermore, several immune responses to suppress pulmonary pathogens can damage the airway epithelial cells, particularly the vital alveolar epithelial cells (pneumocytes). The lungs have a sequentially activated, but overlapping, five phase immune response to suppress most pathogens, while causing minimal damage to the airway epithelial cells. Each phase of the immune response may suppress the pathogens, but if the previous phase proves inadequate, a stronger phase of immune response is activated, but with an increased risk of airway epithelial cell damage. The first phase immune response involves the pulmonary surfactants, which have proteins and phospholipids with potentially sufficient antibacterial, antifungal and antiviral properties to suppress many pathogens. The second phase immune response involves the type III interferons, having pathogen responses with comparatively minimal risk of damage to airway epithelial cells. The third phase immune response involves type I interferons, which implement stronger immune responses against pathogens with an increased risk of damage to airway epithelial cells. The fourth phase immune response involves the type II interferon, interferon-γ, which activates stronger immune responses, but with considerable risk of airway epithelial cell damage. The fifth phase immune response involves antibodies, potentially activating the complement system. In summary, five major phases of immune responses for the lungs are sequentially initiated to create an overlapping immune response which can suppress most pathogens, while usually causing minimal damage to the airway epithelial cells, including the pneumocytes.

Keywords:  Alveolar epithelial cells; Pneumocytes; Respiratory system; Type I interferons; Type II interferons; Type III interferons

DOI:  https://doi.org/10.1007/s10238-023-01083-4
Front Cell Infect Microbiol. 2023 ;13 1149679

The gut microbiome: A line of defense against tuberculosis development.

Ziqi Yu, Xiang Shen, Aiyao Wang, Chong Hu, Jianyong Chen.

  The tuberculosis (TB) burden remains a significant global public health concern, especially in less developed countries. While pulmonary tuberculosis (PTB) is the most common form of the disease, extrapulmonary tuberculosis, particularly intestinal TB (ITB), which is mostly secondary to PTB, is also a significant issue. With the development of sequencing technologies, recent studies have investigated the potential role of the gut microbiome in TB development. In this review, we summarized studies investigating the gut microbiome in both PTB and ITB patients (secondary to PTB) compared with healthy controls. Both PTB and ITB patients show reduced gut microbiome diversity characterized by reduced Firmicutes and elevated opportunistic pathogens colonization; Bacteroides and Prevotella were reported with opposite alteration in PTB and ITB patients. The alteration reported in TB patients may lead to a disequilibrium in metabolites such as short-chain fatty acid (SCFA) production, which may recast the lung microbiome and immunity via the "gut-lung axis". These findings may also shed light on the colonization of Mycobacterium tuberculosis in the gastrointestinal tract and the development of ITB in PTB patients. The findings highlight the crucial role of the gut microbiome in TB, particularly in ITB development, and suggest that probiotics and postbiotics might be useful supplements in shaping a balanced gut microbiome during TB treatment.

Keywords:  Bacteroidetes; Firmicutes; Mycobacterium tuberculosis; gut microbiome; short-chain fatty acids; tuberculosis

DOI:  https://doi.org/10.3389/fcimb.2023.1149679
Cell Metab. 2023 May 02. pii: S1550-4131(23)00135-3. [Epub ahead of print]35(5): 734-736

Energy saver: Monocytes hibernate in bone marrow upon fasting.

Jan Tuckermann, Pamela Fischer-Posovszky.

Immune functions are influenced by the nutritional state. In a recent publication in Immunity, Janssen et al. unveil that a fasting-induced glucocorticoid release makes monocytes move from blood into the bone marrow. Upon refeeding, these chronologically older monocytes are again released and exert detrimental effects during bacterial infection.

DOI: https://doi.org/10.1016/j.cmet.2023.04.008
Benef Microbes. 2023 May 01. 1-14

Post-immunobiotics increase resistance to primary respiratory syncytial virus infection and secondary pneumococcal pneumonia.

F Raya Tonetti, M Tomokiyo, K Fukuyama, M Elean, R Ortiz Moyano, H Yamamuro, R Shibata, S Quilodran-Vega, S Kurata, J Villena, H Kitazawa.

  Previously, we demonstrated that post-immunobiotics derived from Lactobacillus gasseri TMT36, TMT39, and TMT40 strains (HK36, HK39 and HK40, respectively) differentially regulated Toll-like receptor 3 (TLR3)-mediated antiviral respiratory immunity in infant mice. In this work, we investigated whether the HK36, HK39 and HK40 nasal treatments were able to improve the resistance against primary respiratory syncytial virus (RSV) infection and secondary pneumococcal pneumonia. Our results demonstrated that the three treatments increased the resistance to primary viral infection by reducing variations in body weight, RSV titers and lung damage of infected infant mice. Post-immunobiotics significantly enhanced the expressions of interferon (IFN)-λ, IFN-β, IFN-γ, interleukin(IL) - 1β, IL-6, IL-27, Mx1, RNAseL and 2'-5'-oligoadenylate synthetase 1 (OAS1) genes and decreased tumour necrosis factor (TNF)-α in alveolar macrophages of RSV-challenged mice. In addition, the studies in the model of RSV-Streptococcus pneumoniae superinfection showed that the HK39 and HK40 treatments were capable of reducing lung damage, lung bacterial cell counts, and the dissemination of S. pneumoniae into the blood of infant mice. The protective effect was associated with increases in IFN-β, IFN-γ, IL-10, and IL-27 in the respiratory tract. This study demonstrates that the nasal application of the post-immunobiotics HK39 and HK40 stimulates innate respiratory immunity and enhances the defences against primary RSV infection and secondary pneumococcal pneumonia offering an alternative to combat respiratory superinfections in children, which can be fatal.

Keywords:  Lactobacillus gasseri; Streptococcus pneumoniae; antiviral immunity; post-immunobiotics; postbiotics; respiratory superinfection; respiratory syncytial virus

DOI:  https://doi.org/10.3920/BM2022.0118
Front Immunol. 2023 ;14 1130662

The influence of high glucose conditions on macrophages and its effect on the autophagy pathway.

Emanuella S A Sousa, Luiz A D Queiroz, João P T Guimarães, Kamilla C Pantoja, Rafael S Barros, Sabrina Epiphanio, Joilson O Martins.

   Introduction: Macrophages are central cells in mediating the inflammatory response.
Objective and Methods: We evaluated the effect of high glucose conditions on the inflammatory profile and the autophagy pathway in Bone-Marrow Derived Macrophages (BMDM) from diabetic (D-BMDM) (alloxan: 60mg/kg, i.v.) and non-diabetic (ND-BMDM) C57BL/6 mice. BMDM were cultured in medium with normal glucose (5.5 mM), or high glucose (25 mM) concentration and were primed with Nigericin (20µM) stimulated with LPS (100 ng/mL) at times of 30 minutes; 2; 4; 6 and 24 hours, with the measurement of IL-6, IL-1β and TNF-α cytokines.
Results: We have further identified changes in the secretion of pro-inflammatory cytokines IL-6, IL-1β and TNF-α, where BMDM showed increased secretion of these cytokines after LPS + Nigericin stimulation. In addition, changes were observed in the autophagy pathway, where the increase in the autophagic protein LC3b and Beclin-1 occurred by macrophages of non-diabetic animals in hyperglycemic medium, without LPS stimulation. D-BMDM showed a reduction on the expression of LC3b and Beclin-1, suggesting an impaired autophagic process in these cells.
Conclusion: The results suggest that hyperglycemia alters the inflammatory pathways in macrophages stimulated by LPS, playing an important role in the inflammatory response of diabetic individuals.

Keywords:  autophagy; diabetes mellitus; hyperglycemia; inflammation; macrophages

DOI:  https://doi.org/10.3389/fimmu.2023.1130662
Nat Microbiol. 2023 May;8(5): 749-750

Host-pathogen biology intertwines in recurrent UTI.

DOI: https://doi.org/10.1038/s41564-023-01391-1
Sci Rep. 2023 May 03. 13(1): 7207

Ultraviolet exposure regulates skin metabolome based on the microbiome.

Vijaykumar Patra, Natalie Bordag, Yohann Clement, Harald Köfeler, Jean-Francois Nicolas, Marc Vocanson, Sophie Ayciriex, Peter Wolf.

Skin metabolites (< 1500 Da) play a critical role in barrier function, hydration, immune response, microbial invasion, and allergen penetration. We aimed to understand the global metabolic profile changes of the skin in relation to the microbiome and UV exposure and exposed germ-free (devoid of microbiome), disinfected mice (partially devoid of skin microbiome) and control mice with intact microbiome to immunosuppressive doses of UVB radiation. Targeted and untargeted lipidome and metabolome profiling was performed with skin tissue by high-resolution mass spectrometry. UV differentially regulated various metabolites such as alanine, choline, glycine, glutamine, and histidine in germ-free mice compared to control mice. Membrane lipid species such as phosphatidylcholine, phosphatidylethanolamine, and sphingomyelin were also affected by UV in a microbiome-dependent manner. These results shed light on the dynamics and interactions between the skin metabolome, microbiome, and UV exposure and open new avenues for the development of metabolite- or lipid-based applications to maintain skin health.

DOI: https://doi.org/10.1038/s41598-023-34073-3
Endocr Metab Immune Disord Drug Targets. 2023 May 02.

An insight into the combination of probiotics and their implications for human health.

El Bethel Lalthavel Hmar, Sujata Paul, Hemanta Kumar Sharma.

  Over 100-1000 microbial species reside in the human gut, where they predominantly influence the host's internal environment and, thus, have a significant impact on host health. Probiotics are best characterized as a microbe or a group of microbes that reside in the gut and support the body's internal microbiota. Probiotics are linked to increased health advantages, including better immune function, improved nutritional absorption, and protection against cancer and heart-related illnesses. Several studies have demonstrated that combining probiotics from different strains with complementary activities may have synergistic advantages and aid in re-establishing the equilibrium of how immunological niches and microorganisms interact. Another thing to remember is that even though a product contains more probiotic strains, that doesn't always guarantee that the health benefits will be more significant. For specific combinations to be justified, there must be clinical proof. The clinical results of a probiotic strain are specifically pertinent to the participants in the relevant research, such as studies on adults or newborn infants. Clinical outcomes of a probiotic strain are mainly connected to the investigated health area (such as gut health, immune health, oral health, etc.). As a result, picking the right probiotic is essential yet tricky because of several factors, including probiotic products with the disease and strain-specific effectiveness exists; however, various probiotic strains have diverse modes of action. The current review focuses on probiotic categorization, their function in enhancing human health, and any potential health benefits of probiotic combinations.

Keywords:  Bifidobacteria; Dysbiosis; Gut microbiome; Lactic acid bacteria; Lactobacillus

DOI:  https://doi.org/10.2174/1871530323666230502141717
Front Cell Infect Microbiol. 2023 ;13 1092317

Metabolic pathways that permit Mycobacterium avium subsp. hominissuis to transition to different environments encountered within the host during infection.

Norah Abukhalid, Rajoana Rojony, Lia Danelishvili, Luiz E Bermudez.

   Introduction: M. avium subsp. hominissuis (M. avium) is an intracellular, facultative bacterium known to colonize and infect the human host through ingestion or respiratory inhalation. The majority of pulmonary infections occur in association with pre- existing lung diseases, such as bronchiectasis, cystic fibrosis, or chronic obstructive pulmonary disease. M. avium is also acquired by the gastrointestinal route in immunocompromised individuals such as human immunodeficiency virus HIV-1 patients leading to disseminated disease. A hallmark of M. avium pulmonary infections is the ability of pathogen to form biofilms. In addition, M. avium can reside within granulomas of low oxygen and limited nutrient conditions while establishing a persistent niche through metabolic adaptations.
Methods: Bacterial metabolic pathways used by M. avium within the host environment, however, are poorly understood. In this study, we analyzed M. avium proteome with a focus on core metabolic pathways expressed in the anaerobic, biofilm and aerobic conditions and that can be used by the pathogen to transition from one environment to another.
Results: Overall, 3,715 common proteins were identified between all studied conditions and proteins with increased synthesis over the of the level of expression in aerobic condition were selected for analysis of in specific metabolic pathways. The data obtained from the M. avium proteome of biofilm phenotype demonstrates in enrichment of metabolic pathways involved in the fatty acid metabolism and biosynthesis of aromatic amino acid and cofactors. Here, we also highlight the importance of chloroalkene degradation pathway and anaerobic fermentationthat enhance during the transition of M. avium from aerobic to anaerobic condition. It was also found that the production of fumarate and succinate by MAV_0927, a conserved hypothetical protein, is essential for M. avium survival and for withstanding the stress condition in biofilm. In addition, the participation of regulatory genes/proteins such as the TetR family MAV_5151 appear to be necessary for M. avium survival under biofilm and anaerobic conditions.
Conclusion: Collectively, our data reveal important core metabolic pathways that M. avium utilize under different stress conditions that allow the pathogen to survive in diverse host environments.

Keywords:  M. avium; aerobic; anaerobic; biofilm; metabolic pathways; proteomics; stress conditions

DOI:  https://doi.org/10.3389/fcimb.2023.1092317
Front Immunol. 2023 ;14 1160035

Mitochondria in innate immunity signaling and its therapeutic implications in autoimmune diseases.

Yuhao Jiao, Zhiyu Yan, Aiming Yang.

  Autoimmune diseases are characterized by vast alterations in immune responses, but the pathogenesis remains sophisticated and yet to be fully elucidated. Multiple mechanisms regulating cell differentiation, maturation, and death are critical, among which mitochondria-related cellular organelle functions have recently gained accumulating attention. Mitochondria, as a highly preserved organelle in eukaryotes, have crucial roles in the cellular response to both exogenous and endogenous stress beyond their fundamental functions in chemical energy conversion. In this review, we aim to summarize recent findings on the function of mitochondria in the innate immune response and its aberrancy in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, etc., mainly focusing on its direct impact on cellular metabolism and its machinery on regulating immune response signaling pathways. More importantly, we summarize the status quo of potential therapeutic targets found in the mitochondrial regulation in the setting of autoimmune diseases and wish to shed light on future studies.

Keywords:  autoimmune disease; immune metabolism; innate immunity; mitochondria; therapeutic targets

DOI:  https://doi.org/10.3389/fimmu.2023.1160035
Lab Anim (NY). 2023 May;52(5): 102

A new mouse model to study the early-life microbiome.

Alexandra Le Bras.

DOI: https://doi.org/10.1038/s41684-023-01176-3
Adv Biol (Weinh). 2023 May 04. e2300100

The Role of Diet and Gut Microbiota Interactions in Metabolic Homeostasis.

Lizhi Guan, Ruixin Liu.

  Diet is a pivotal determinant in shaping the structure and function of resident microorganisms in the gut through different food components, nutritive proportion, and calories. The effects of diet on host metabolism and physiology can be mediated through the gut microbiota. Gut microbiota-derived metabolites have been shown to regulate glucose and lipid metabolism, energy consumption, and the immune system. On the other hand, emerging evidence indicates that baseline gut microbiota could predict the efficacy of diet intervention, highlighting gut microbiota can be harnessed as a biomarker in personalized nutrition. In this review, the alterations of gut microbiota in different dietary components and dietary patterns, and the potential mechanisms in the diet-microbiota crosstalk are summarized to understand the interactions of diet and gut microbiota on the impact of metabolic homeostasis.

Keywords:  dietary pattern; gut microbiome; macronutrients; metabolism; personalized nutrition

DOI:  https://doi.org/10.1002/adbi.202300100