bims-bac4me 2023-03-12 papers

bims-bac4me

Biomed News

on Microbiome and trained immunity

Issue of 2023–03–12
twenty papers selected by
Chun-Chi Chang, University Hospital Zurich

Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease.
"Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system.
Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma.
Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin.
Macrophage Polarization: An Important Candidate Regulator for Lung Diseases.
Bacterial flagellin is a dominant, stable innate immune activator in the gastrointestinal contents of mice and rats.
The Intestinal and Skin Microbiome in Patients with Atopic Dermatitis and Their Influence on the Course of the Disease: A Literature Review.
Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?
Pulmonary and Non-Pulmonary Sepsis Differentially Modulate Lung Immunity Towards Secondary Bacterial Pneumonia: A Critical Role for Alveolar Macrophages.
Immunomodulatory role of oral microbiota in inflammatory diseases and allergic conditions.
NF-κB-Inducing Kinase Governs the Mitochondrial Respiratory Capacity, Differentiation, and Inflammatory Status of Innate Immune Cells.
Naturally-occurring serotype 3 Streptococcus pneumoniae strains that lack functional pneumolysin and autolysin have attenuated virulence but induce localized protective immune responses.
Editorial: The interplay between microbiota and allergen in shaping respiratory mucosa immunity: Role in development of asthma.
Fine particulate matter (PM2.5) induces inhibitory memory alveolar macrophages through the AhR/IL-33 pathway.
Genomic analysis of Staphylococcus aureus sequential isolates from lungs of patients with cystic fibrosis.
The Cystic Fibrosis Upper and Lower Airway Metagenome.
Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions.
Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis.
Alteration of gut microbiome and metabolome by Clostridium butyricum can repair the intestinal dysbiosis caused by antibiotics in mice.
Lactobacillus for the treatment and prevention of atopic dermatitis: Clinical and experimental evidence.

Front Pharmacol. 2023 ;14 1109576

Trained immunity in monocyte/macrophage: Novel mechanism of phytochemicals in the treatment of atherosclerotic cardiovascular disease.

Jie Wang, Yong-Mei Liu, Jun Hu, Cong Chen.

  Atherosclerosis (AS) is the pathology of atherosclerotic cardiovascular diseases (ASCVD), characterized by persistent chronic inflammation in the vessel wall, in which monocytes/macrophages play a key role. It has been reported that innate immune system cells can assume a persistent proinflammatory state after short stimulation with endogenous atherogenic stimuli. The pathogenesis of AS can be influenced by this persistent hyperactivation of the innate immune system, which is termed trained immunity. Trained immunity has also been implicated as a key pathological mechanism, leading to persistent chronic inflammation in AS. Trained immunity is mediated via epigenetic and metabolic reprogramming and occurs in mature innate immune cells and their bone marrow progenitors. Natural products are promising candidates for novel pharmacological agents that can be used to prevent or treat cardiovascular diseases (CVD). A variety of natural products and agents exhibiting antiatherosclerotic abilities have been reported to potentially interfere with the pharmacological targets of trained immunity. This review describes in as much detail as possible the mechanisms involved in trained immunity and how phytochemicals of this process inhibit AS by affecting trained monocytes/macrophages.

Keywords:  atherosclerosis; epigenetic reprogramming; metabolic reprogramming; monocyte/macrophage; natural products; trained immunity

DOI:  https://doi.org/10.3389/fphar.2023.1109576
Semin Immunol. 2023 Mar 04. pii: S1044-5323(23)00029-5. [Epub ahead of print]66 101738

"Under Pressure" - How fungi evade, exploit, and modulate cells of the innate immune system.

Theresa Lange, Lydia Kasper, Mark S Gresnigt, Sascha Brunke, Bernhard Hube.

  The human immune system uses an arsenal of effector mechanisms to prevent and counteract infections. Yet, some fungal species are extremely successful as human pathogens, which can be attributed to a wide variety of strategies by which these fungi evade, exploit, and modulate the immune system. These fungal pathogens normally are either harmless commensals or environmental fungi. In this review we discuss how commensalism, but also life in an environmental niche without human contact, can drive the evolution of diverse and specialized immune evasion mechanisms. Correspondingly, we discuss the mechanisms contributing to the ability of these fungi to cause superficial to life-threatening infections.

Keywords:  Evolution; Host-pathogen interactions; Human fungal pathogens; Immune evasion; Macrophages

DOI:  https://doi.org/10.1016/j.smim.2023.101738
J Invest Dermatol. 2023 Mar 06. pii: S0022-202X(23)00175-6. [Epub ahead of print]

Endolysin inhibits skin colonization by patient-derived Staphylococcus aureus and malignant T cell activation in cutaneous T cell lymphoma.

Emil M H Pallesen, Maria Gluud, Chella K Vadivel, Terkild B Buus, Bob de Rooij, Ziao Zeng, Sana Ahmad, Andreas Willerslev-Olsen, Christian Röhrig, Maria R Kamstrup, Lene Bay, Lise Lindahl, Thorbjørn Krejsgaard, Carsten Geisler, Charlotte M Bonefeld, Lars Iversen, Anders Woetmann, Sergei B Koralov, Thomas Bjarnsholt, Johan Frieling, Mathias Schmelcher, Niels Ødum.

Staphylococcus aureus (S. aureus) is suspected to fuel disease activity in cutaneous T cell lymphomas (CTCL). Here we investigate the effect of a recombinant, anti-bacterial protein, endolysin, XZ.700, on S. aureus skin colonization and malignant T cell activation. We show that endolysin strongly inhibits proliferation of S. aureus isolated from CTCL skin and significantly decreases S. aureus bacterial cell counts in a dose-dependent manner. Likewise, ex vivo colonization of both healthy and lesional skin by S. aureus is profoundly inhibited by endolysin. Moreover, endolysin inhibits the patient-derived S. aureus induction of Interferon-gamma (IFNγ) and IFNγ-inducible chemokine CXCL10 in healthy skin. Whereas patient-derived S. aureus stimulates activation and proliferation of malignant T cells in vitro through an indirect mechanism involving non-malignant T cells, endolysin strongly inhibits the effects of S. aureus on activation (reduced CD25 and STAT5 phosphorylation) and proliferation (reduced Ki67) of malignant T cells and cell lines in the presence of non-malignant T cells. Taken together, we provide evidence that endolysin XZ.700 inhibits skin colonization, chemokine expression, and proliferation of pathogenic S. aureus, and blocks their potential tumor-promoting effects on malignant T cells.

DOI: https://doi.org/10.1016/j.jid.2023.01.039
J Clin Med. 2023 Mar 01. pii: 1941. [Epub ahead of print]12(5):

Th2 Cytokines Affect the Innate Immune Barrier without Impairing the Physical Barrier in a 3D Model of Normal Human Skin.

Elena Donetti, Federica Riva, Serena Indino, Giulia Lombardo, Franz Baruffaldi Preis, Elia Rosi, Francesca Prignano.

  (1) Background: Atopic dermatitis is one of the most common inflammatory skin diseases characterized by T helper (Th) 2 and Th22 cells producing interleukin (IL)-4/IL-13 and IL-22, respectively. The specific contribution of each cytokine to the impairment of the physical and the immune barrier via Toll-like receptors (TLRs) is poorly addressed concerning the epidermal compartment of the skin. (2) Methods: The effect of IL-4, IL-13, IL-22, and the master cytokine IL-23 is evaluated in a 3D model of normal human skin biopsies (n = 7) at the air-liquid interface for 24 and 48 h. We investigated by immunofluorescence the expressions of (i) claudin-1, zonula occludens (ZO)-1 filaggrin, involucrin for the physical barrier and (ii) TLR2, 4, 7, 9, human beta-defensin 2 (hBD-2) for the immune barrier. (3) Results: Th2 cytokines induce spongiosis and fail in impairing tight junction composition, while IL-22 reduces and IL-23 induces claudin-1 expression. IL-4 and IL-13 affect the TLR-mediated barrier largely than IL-22 and IL-23. IL-4 early inhibits hBD-2 expression, while IL-22 and IL-23 induce its distribution. (4) Conclusions: This experimental approach looks to the pathogenesis of AD through molecular epidermal proteins rather than cytokines only and paves the way for tailored patient therapy.

Keywords:  claudin-1; filaggrin; human beta-defensin 2; human epidermis; immunofluorescence; interleukins; involucrin; keratinocytes; toll-like receptors; transmission electron microscopy

DOI:  https://doi.org/10.3390/jcm12051941
Molecules. 2023 Mar 04. pii: 2379. [Epub ahead of print]28(5):

Macrophage Polarization: An Important Candidate Regulator for Lung Diseases.

Lishuang Deng, Zhijie Jian, Tong Xu, Fengqin Li, Huidan Deng, Yuancheng Zhou, Siyuan Lai, Zhiwen Xu, Ling Zhu.

  Macrophages are crucial components of the immune system and play a critical role in the initial defense against pathogens. They are highly heterogeneous and plastic and can be polarized into classically activated macrophages (M1) or selectively activated macrophages (M2) in response to local microenvironments. Macrophage polarization involves the regulation of multiple signaling pathways and transcription factors. Here, we focused on the origin of macrophages, the phenotype and polarization of macrophages, as well as the signaling pathways associated with macrophage polarization. We also highlighted the role of macrophage polarization in lung diseases. We intend to enhance the understanding of the functions and immunomodulatory features of macrophages. Based on our review, we believe that targeting macrophage phenotypes is a viable and promising strategy for treating lung diseases.

Keywords:  M1/M2; lung disease; macrophage; polarization; signaling pathway

DOI:  https://doi.org/10.3390/molecules28052379
Gut Microbes. 2023 Jan-Dec;15(1):15(1): 2185031

Bacterial flagellin is a dominant, stable innate immune activator in the gastrointestinal contents of mice and rats.

Matam Vijay-Kumar, Venugopal R Bovilla, Beng San Yeoh, Rachel M Golonka, Piu Saha, Bina Joe, Andrew T Gewirtz.

  Intestinal contents comprise the largest repository of immunogenic ligands of microbial origin. We undertook this study to assess the predominant microbe-associated molecular patterns (MAMPs) present therein and the receptors) that mediate the innate immune responses to them. Here, we demonstrated that intestinal contents from conventional, but not germ-free, mice and rats triggered robust innate immune responses in vitro and in vivo. Such immune responses were abrogated in the absence of either myeloid differentiation factor 88 (MyD88) or Toll-like receptor (TLR) 5, but not TLR4, suggesting that the stimuli was flagellin (i.e., protein subunit of flagella that drives bacterial motility). Accordingly, pre-treating intestinal extracts with proteinase, thereby degrading flagellin, was sufficient to block their ability to activate innate immune responses. Taken together, this work serves to underscore flagellin as a major, heat-stable and bioactive MAMP in the intestinal content that confers this milieu strong potential to trigger innate immune responses.

Keywords:  Gut microbiota; IL-10; LPS; MyD88; cytokines; toll-like Receptor-4; toll-like Receptor-5

DOI:  https://doi.org/10.1080/19490976.2023.2185031
Healthcare (Basel). 2023 Mar 06. pii: 766. [Epub ahead of print]11(5):

The Intestinal and Skin Microbiome in Patients with Atopic Dermatitis and Their Influence on the Course of the Disease: A Literature Review.

Małgorzata Mazur, Hanna Tomczak, Martha Łodyga, Katarzyna Plagens-Rotman, Piotr Merks, Magdalena Czarnecka-Operacz.

  Bacteria inhabiting the digestive tract are responsible for our health. The microbiome is essential for the development of the immune system and homeostasis of the body. Maintaining homeostasis is very important, but also extremely complicated. The gut microbiome is related to the skin microbiome. It can therefore be assumed that changes in the microbes inhabiting the skin are greatly influenced by the bacteria living in the intestines. Changes in the composition and function of microbes (dysbiosis in the skin and intestines) have recently been linked to changes in the immune response and the development of skin diseases, including atopic dermatitis (AD). This review was compiled by collaborating Dermatologists specializing in atopic dermatitis and psoriasis. A comprehensive review of the current literature was performed using PubMed and limited to relevant case reports and original papers on the skin microbiome in atopic dermatitis. The inclusion criterion was that the paper was published in a peer-reviewed journal in the last 10 years (2012-2022). No limitations on the language of the publication or the type of study were made. It has been shown that any rapid changes in the composition of the microflora may be associated with the appearance of clinical signs and symptoms of the disease. Various studies have proven that the microbiome of many systems (including the intestines) may have a significant impact on the development of the inflammatory process within the skin in the course of AD. It has been shown that an early interaction between the microbiome and immune system may result in a noticeable delay in the onset of atopic diseases. It seems to be of high importance for physicians to understand the role of the microbiome in AD, not only from the pathophysiological standpoint but also in terms of the complex treatment that is required. Perhaps young children diagnosed with AD present specific characteristics of the intestinal microflora. This might be related to the early introduction of antibiotics and dietary manipulations in breastfeeding mothers in the early childhood of AD patients. It is most likely related to the abuse of antibiotics from the first days of life.

Keywords:  atopic dermatitis; microbiome

DOI:  https://doi.org/10.3390/healthcare11050766
Front Immunol. 2023 ;14 1108289

Understanding disruption of the gut barrier during inflammation: Should we abandon traditional epithelial cell lines and switch to intestinal organoids?

Susana Lechuga, Manuel B Braga-Neto, Nayden G Naydenov, Florian Rieder, Andrei I Ivanov.

  Disruption of the intestinal epithelial barrier is a hallmark of mucosal inflammation. It increases exposure of the immune system to luminal microbes, triggering a perpetuating inflammatory response. For several decades, the inflammatory stimuli-induced breakdown of the human gut barrier was studied in vitro by using colon cancer derived epithelial cell lines. While providing a wealth of important data, these cell lines do not completely mimic the morphology and function of normal human intestinal epithelial cells (IEC) due to cancer-related chromosomal abnormalities and oncogenic mutations. The development of human intestinal organoids provided a physiologically-relevant experimental platform to study homeostatic regulation and disease-dependent dysfunctions of the intestinal epithelial barrier. There is need to align and integrate the emerging data obtained with intestinal organoids and classical studies that utilized colon cancer cell lines. This review discusses the utilization of human intestinal organoids to dissect the roles and mechanisms of gut barrier disruption during mucosal inflammation. We summarize available data generated with two major types of organoids derived from either intestinal crypts or induced pluripotent stem cells and compare them to the results of earlier studies with conventional cell lines. We identify research areas where the complementary use of colon cancer-derived cell lines and organoids advance our understanding of epithelial barrier dysfunctions in the inflamed gut and identify unique questions that could be addressed only by using the intestinal organoid platforms.

Keywords:  actin cytoskeleton; adherens junctions; colonoids; cytokines; enteroids; epithelial barrier; inflammatory bowel diseases; tight junctions

DOI:  https://doi.org/10.3389/fimmu.2023.1108289
Am J Respir Cell Mol Biol. 2023 Mar 08.

Pulmonary and Non-Pulmonary Sepsis Differentially Modulate Lung Immunity Towards Secondary Bacterial Pneumonia: A Critical Role for Alveolar Macrophages.

Jean-François Llitjos, Cédric Auffray, Edwige Péju, Zakaria Ait Hamou, Christophe Rousseau, Aurélie Durand, Clémence Martin, Jean-Paul Mira, Pierre-Régis Burgel, Jean-Daniel Chiche, Maha Zohra Ladjemi, Bruno Lucas, Frédéric Pène.

  Clinical observations suggest that the source of primary infection accounts for a major determinant of further nosocomial pneumonia in critically ill sepsis patients. We herein addressed the impact of primary non-pulmonary or pulmonary septic insults on lung immunity using relevant double-hit animal models. C57BL/6J mice were first subjected to either polymicrobial peritonitis induced by caecal ligation and puncture (CLP) or bacterial pneumonia induced by intratracheal challenge with Escherichia coli. Seven days after, post-septic mice received intratracheal challenge with Pseudomonas aeruginosa. When compared to controls, post-CLP mice became highly susceptible to P. aeruginosa pneumonia as demonstrated by defective lung bacterial clearance and increased mortality rate. In contrast, all post-pneumonia mice survived the P. aeruginosa challenge and even exhibited improved bacterial clearance. Non-pulmonary and pulmonary sepsis differentially modulated the amounts and some important immune functions of alveolar macrophages. Additionally, we observed a Toll-like receptor 2 (TLR2)-dependent increase in regulatory T cells (Tregs) in lungs from post-CLP mice. Antibody-mediated Tregs depletion restored the numbers and functions of alveolar macrophages in post-CLP mice. Furthermore, post-CLP TLR2-deficient mice were found resistant to secondary P. aeruginosa pneumonia. In conclusion, polymicrobial peritonitis and bacterial pneumonia conferred susceptibility or resistance to secondary Gram-negative pulmonary infection, respectively. Immune patterns in post-CLP lungs argue for a TLR2-dependent crosstalk between T-regs and alveolar macrophages, as an important regulatory mechanism in post-septic lung defense.

Keywords:  TLR2; Trained immunity; alveolar macrophage; regulatory T cells; sepsis

DOI:  https://doi.org/10.1165/rcmb.2022-0281OC
Front Allergy. 2023 ;4 1067483

Immunomodulatory role of oral microbiota in inflammatory diseases and allergic conditions.

Carlos M Moreno, Ellie Boeree, Claudia M Tellez Freitas, K Scott Weber.

  In recent years, the interplay between oral microbiota and systemic disease has gained attention as poor oral health is associated with several pathologies. The oral microbiota plays a role in the maintenance of overall health, and its dysbiosis influences chronic inflammation and the pathogenesis of gum diseases. Periodontitis has also been associated with other diseases and health complications such as cancer, neurogenerative and autoimmune disorders, chronic kidney disease, cardiovascular diseases, rheumatic arthritis, respiratory health, and adverse pregnancy outcomes. The host microbiota can influence immune cell development and immune responses, and recent evidence suggests that changes in oral microbiota composition may also contribute to sensitization and the development of allergic reactions, including asthma and peanut allergies. Conversely, there is also evidence that allergic reactions within the gut may contribute to alterations in oral microbiota composition. Here we review the current evidence of the role of the oral microbiota in inflammatory diseases and health complications, as well as its future relevance in improving health and ameliorating allergic disease.

Keywords:  allergy; local inflammation; microbiota; oral microbiome; oral microbiota; systemic inflammation

DOI:  https://doi.org/10.3389/falgy.2023.1067483
J Immunol. 2023 Mar 06. pii: ji2200596. [Epub ahead of print]

NF-κB-Inducing Kinase Governs the Mitochondrial Respiratory Capacity, Differentiation, and Inflammatory Status of Innate Immune Cells.

Justin N Keeney, Ashley A Winters, Raquel Sitcheran, A Phillip West.

NF-κB-inducing kinase (NIK), which is essential for the activation of the noncanonical NF-κB pathway, regulates diverse processes in immunity, development, and disease. Although recent studies have elucidated important functions of NIK in adaptive immune cells and cancer cell metabolism, the role of NIK in metabolic-driven inflammatory responses in innate immune cells remains unclear. In this study, we demonstrate that murine NIK-deficient bone marrow-derived macrophages exhibit defects in mitochondrial-dependent metabolism and oxidative phosphorylation, which impair the acquisition of a prorepair, anti-inflammatory phenotype. Subsequently, NIK-deficient mice exhibit skewing of myeloid cells characterized by aberrant eosinophil, monocyte, and macrophage cell populations in the blood, bone marrow, and adipose tissue. Furthermore, NIK-deficient blood monocytes display hyperresponsiveness to bacterial LPS and elevated TNF-α production ex vivo. These findings suggest that NIK governs metabolic rewiring, which is critical for balancing proinflammatory and anti-inflammatory myeloid immune cell function. Overall, our work highlights a previously unrecognized role for NIK as a molecular rheostat that fine-tunes immunometabolism in innate immunity, and suggests that metabolic dysfunction may be an important driver of inflammatory diseases caused by aberrant NIK expression or activity.

DOI: https://doi.org/10.4049/jimmunol.2200596
PLoS One. 2023 ;18(3): e0282843

Naturally-occurring serotype 3 Streptococcus pneumoniae strains that lack functional pneumolysin and autolysin have attenuated virulence but induce localized protective immune responses.

Ηαnnah E Wong, Panagiotis Tourlomousis, Gavin K Paterson, Steve Webster, Clare E Bryant.

Streptococcus pneumoniae is an important cause of fatal pneumonia in humans. These bacteria express virulence factors, such as the toxins pneumolysin and autolysin, that drive host inflammatory responses. In this study we confirm loss of pneumolysin and autolysin function in a group of clonal pneumococci that have a chromosomal deletion resulting in a pneumolysin-autolysin fusion gene Δ(lytA'-ply')593. The Δ(lytA'-ply')593 pneumococci strains naturally occur in horses and infection is associated with mild clinical signs. Here we use immortalized and primary macrophage in vitro models, which include pattern recognition receptor knock-out cells, and a murine acute pneumonia model to show that a Δ(lytA'-ply')593 strain induces cytokine production by cultured macrophages, however, unlike the serotype-matched ply+lytA+ strain, it induces less tumour necrosis factor α (TNFα) and no interleukin-1β production. The TNFα induced by the Δ(lytA'-ply')593 strain requires MyD88 but, in contrast to the ply+lytA+ strain, is not reduced in cells lacking TLR2, 4 or 9. In comparison to the ply+lytA+ strain in a mouse model of acute pneumonia, infection with the Δ(lytA'-ply')593 strain resulted in less severe lung pathology, comparable levels of interleukin-1α, but minimal release of other pro-inflammatory cytokines, including interferon-γ, interleukin-6 and TNFα. These results suggest a mechanism by which a naturally occurring Δ(lytA'-ply')593 mutant strain of S. pneumoniae that resides in a non-human host has reduced inflammatory and invasive capacity compared to a human S. pneumoniae strain. These data probably explain the relatively mild clinical disease in response to S. pneumoniae infection seen in horses in comparison to humans.

DOI: https://doi.org/10.1371/journal.pone.0282843
Front Immunol. 2023 ;14 1131215

Editorial: The interplay between microbiota and allergen in shaping respiratory mucosa immunity: Role in development of asthma.

Zhenwei Xia, Wenwei Zhong, Min Wu, Scott E Evans.



Keywords:  airway inflammation; antibiotics; asthma; dendric cells; invariant natural killer cells; β2-adrenergic receptors

DOI:  https://doi.org/10.3389/fimmu.2023.1131215
Cell Immunol. 2023 Feb 23. pii: S0008-8749(23)00033-3. [Epub ahead of print]386 104694

Fine particulate matter (PM2.5) induces inhibitory memory alveolar macrophages through the AhR/IL-33 pathway.

Yanan Liu, Qi Yuan, Xijie Zhang, Zhongqi Chen, Xinyu Jia, Min Wang, Tingting Xu, Zhengxia Wang, Jingxian Jiang, Qiyun Ma, Mingshun Zhang, Mao Huang, Ningfei Ji.

  Fine particulate matter (PM2.5) concentrations have decreased in the past decade. The adverse effects of acute PM2.5 exposure on respiratory diseases have been well recognized. To explore the long-term effects of PM2.5 exposure on chronic obstructive pulmonary disease (COPD), mice were exposed to PM2.5 for 7 days and rest for 21 days, followed by challenges with lipopolysaccharide (LPS) and porcine pancreatic elastase (PPE). Unexpectedly, PM2.5 exposure and rest alleviated the disease severity and airway inflammatory responses in COPD-like mice. Although acute PM2.5 exposure increased airway inflammation, rest for 21 days reversed the airway inflammatory responses, which was associated with the induction of inhibitory memory alveolar macrophages (AMs). Similarly, polycyclic aromatic hydrocarbons (PAHs) in PM2.5 exposure and rest decreased pulmonary inflammation, accompanied by inhibitory memory AMs. Once AMs were depleted, pulmonary inflammation was aggravated. PAHs in PM2.5 promoted the secretion of IL-33 from airway epithelial cells via the aryl hydrocarbon receptor (AhR)/ARNT pathway. High-throughput mRNA sequencing revealed that PM2.5 exposure and rest drastically changed the mRNA profiles in AMs, which was largely rescued in IL-33-/- mice. Collectively, our results indicate that PM2.5 may mitigate pulmonary inflammation, which is mediated by inhibitory trained AMs via IL-33 production from epithelial cells through the AhR/ARNT pathway. We provide the rationale that PM2.5 plays complicated roles in respiratory disease.

Keywords:  AhR; Alveolar macrophages; COPD; IL-33; PM2.5; Trained immunity

DOI:  https://doi.org/10.1016/j.cellimm.2023.104694
Microbes Infect. 2023 Mar 03. pii: S1286-4579(23)00027-8. [Epub ahead of print] 105124

Genomic analysis of Staphylococcus aureus sequential isolates from lungs of patients with cystic fibrosis.

Xiongqi Ding, Xiali Fu, Daniel Euphrasie, Agnes Ferroni, Isabelle Sermet-Gaudelus, Alain Charbit, Mathieu Coureuil, Anne Jamet.

Staphylococcus aureus is the predominant pathogen in children with cystic fibrosis (CF) in France and, around 80 % of them harbored S. aureus in their lungs. This study investigated virulence and antimicrobial resistance-associated genes and within-host evolution polymorphisms in 14 S. aureus persistent clones from 14 chronically infected CF children. For each of the 14 patients, we compared genomes of two isogenic sequential isolates separated by 2-9 years. All isolates were methicillin-sensitive and harbored the immune evasion gene cluster, whereas half of them harbored the enterotoxin gene cluster. Most clones were capsule type 8 (8/14) and accessory gene regulator (agr)-specificity group 1 (9/14). We identified convergent mutations in genes involved in carbohydrate metabolism, cell wall metabolism, genetic information processing and adhesion, which are likely to play important role in intracellular invasion and persistence. Further explorations relying notably on proteomics will contribute to improve our understanding of the mechanisms at play in the striking long-term persistence ability of S. aureus.

DOI: https://doi.org/10.1016/j.micinf.2023.105124
Microbiol Spectr. 2023 Mar 09. e0363322

The Cystic Fibrosis Upper and Lower Airway Metagenome.

Katarzyna Pienkowska, Marie-Madlen Pust, Margaux Gessner, Svenja Gaedcke, Ajith Thavarasa, Ilona Rosenboom, Patricia Morán Losada, Rebecca Minso, Christin Arnold, Silke Hedtfeld, Marie Dorda, Lutz Wiehlmann, Jochen G Mainz, Jens Klockgether, Burkhard Tümmler.

  The microbial metagenome in cystic fibrosis (CF) airways was investigated by whole-genome shotgun sequencing of total DNA isolated from nasal lavage samples, oropharyngeal swabs, and induced sputum samples collected from 65 individuals with CF aged 7 to 50 years. Each patient harbored a personalized microbial metagenome unique in microbial load and composition, the exception being monocultures of the most common CF pathogens Staphylococcus aureus and Pseudomonas aeruginosa from patients with advanced lung disease. The sampling of the upper airways by nasal lavage uncovered the fungus Malassezia restricta and the bacterium Staphylococcus epidermidis as prominent species. Healthy and CF donors harbored qualitatively and quantitatively different spectra of commensal bacteria in their sputa, even in the absence of any typical CF pathogen. If P. aeruginosa, S. aureus, or Stenotrophomonas maltophilia belonged to the trio of the most abundant species in the CF sputum metagenome, common inhabitants of the respiratory tract of healthy subjects, i.e., Eubacterium sulci, Fusobacterium periodonticum, and Neisseria subflava, were present only in low numbers or not detectable. Random forest analysis identified the numerical ecological parameters of the bacterial community, such as Shannon and Simpson diversity, as the key parameters that globally distinguish sputum samples from CF and healthy donors. IMPORTANCE Cystic fibrosis (CF) is the most common life-limiting monogenetic disease in European populations and is caused by mutations in the CFTR gene. Chronic airway infections with opportunistic pathogens are the major morbidity that determines prognosis and quality of life in most people with CF. We examined the composition of the microbial communities of the oral cavity and upper and lower airways in CF patients across all age groups. From early on, the spectrum of commensals is different in health and CF. Later on, when the common CF pathogens take up residence in the lungs, we observed differential modes of depletion of the commensal microbiota in the presence of S. aureus, P. aeruginosa, S. maltophilia, or combinations thereof. It remains to be seen whether the implementation of lifelong CFTR (cystic fibrosis transmembrane conductance regulator) modulation will change the temporal evolution of the CF airway metagenome.

Keywords:  airways; cystic fibrosis; metagenomics

DOI:  https://doi.org/10.1128/spectrum.03633-22
Front Immunol. 2023 ;14 1126107

Generating enhanced mucosal immunity against Bordetella pertussis: current challenges and new directions.

Amanda D Caulfield, Maiya Callender, Eric T Harvill.

  Bordetella pertussis (Bp) is the highly transmissible etiologic agent of pertussis, a severe respiratory disease that causes particularly high morbidity and mortality in infants and young children. Commonly known as "whooping cough," pertussis is one of the least controlled vaccine-preventable diseases worldwide with several countries experiencing recent periods of resurgence despite broad immunization coverage. While current acellular vaccines prevent severe disease in most cases, the immunity they confer wanes rapidly and does not prevent sub clinical infection or transmission of the bacterium to new and vulnerable hosts. The recent resurgence has prompted new efforts to generate robust immunity to Bp in the upper respiratory mucosa, from which colonization and transmission originate. Problematically, these initiatives have been partially hindered by research limitations in both human and animal models as well as potent immunomodulation by Bp. Here, we consider our incomplete understanding of the complex host-pathogen dynamics occurring in the upper airway to propose new directions and methods that may address critical gaps in research. We also consider recent evidence that supports the development of novel vaccines specifically designed to generate robust mucosal immune responses capable of limiting upper respiratory colonization to finally halt the ongoing circulation of Bordetella pertussis.

Keywords:  animal models; mucosal immunity; pertussis; pulmonary disease; sterilizing immunity; waning immunity; whooping cough

DOI:  https://doi.org/10.3389/fimmu.2023.1126107
Cells. 2023 Mar 02. pii: 793. [Epub ahead of print]12(5):

Gut-Microbiota-Derived Metabolites Maintain Gut and Systemic Immune Homeostasis.

Juanjuan Wang, Ningning Zhu, Xiaomin Su, Yunhuan Gao, Rongcun Yang.

  The gut microbiota, including bacteria, archaea, fungi, viruses and phages, inhabits the gastrointestinal tract. This commensal microbiota can contribute to the regulation of host immune response and homeostasis. Alterations of the gut microbiota have been found in many immune-related diseases. The metabolites generated by specific microorganisms in the gut microbiota, such as short-chain fatty acids (SCFAs), tryptophan (Trp) and bile acid (BA) metabolites, not only affect genetic and epigenetic regulation but also impact metabolism in the immune cells, including immunosuppressive and inflammatory cells. The immunosuppressive cells (such as tolerogenic macrophages (tMacs), tolerogenic dendritic cells (tDCs), myeloid-derived suppressive cells (MDSCs), regulatory T cells (Tregs), regulatory B cells (Breg) and innate lymphocytes (ILCs)) and inflammatory cells (such as inflammatory Macs (iMacs), DCs, CD4 T helper (Th)1, CD4Th2, Th17, natural killer (NK) T cells, NK cells and neutrophils) can express different receptors for SCFAs, Trp and BA metabolites from different microorganisms. Activation of these receptors not only promotes the differentiation and function of immunosuppressive cells but also inhibits inflammatory cells, causing the reprogramming of the local and systemic immune system to maintain the homeostasis of the individuals. We here will summarize the recent advances in understanding the metabolism of SCFAs, Trp and BA in the gut microbiota and the effects of SCFAs, Trp and BA metabolites on gut and systemic immune homeostasis, especially on the differentiation and functions of the immune cells.

Keywords:  SCFAs; bile acid metabolites; gut microbiota; regulatory T cells; tolerogenic macrophages; tryptophan metabolites

DOI:  https://doi.org/10.3390/cells12050793
iScience. 2023 Mar 17. 26(3): 106190

Alteration of gut microbiome and metabolome by Clostridium butyricum can repair the intestinal dysbiosis caused by antibiotics in mice.

Xin Liu, Xiaoyu Qiu, Yong Yang, Jing Wang, Qi Wang, Jingbo Liu, Feiyun Yang, Zuohua Liu, Renli Qi.

  This study evaluated the repair effects of Clostridium butyricum (CBX 2021) on the antibiotic (ABX)-induced intestinal dysbiosis in mice by the multi-omics method. Results showed that ABX eliminated more than 90% of cecal bacteria and also exerted adverse effects on the intestinal structure and overall health in mice after 10 days of the treatment. Of interest, supplementing CBX 2021 in the mice for the next 10 days colonized more butyrate-producing bacteria and accelerated butyrate production compared with the mice by natural recovery. The reconstruction of intestinal microbiota efficiently promoted the improvement of the damaged gut morphology and physical barrier in the mice. In addition, CBX 2021 significantly reduced the content of disease-related metabolites and meanwhile promoted carbohydrate digestion and absorption in mice followed the microbiome alternation. In conclusion, CBX 2021 can repair the intestinal ecology of mice damaged by the antibiotics through reconstructing gut microbiota and optimizing metabolic functions.

Keywords:  Immunology; Medical Microbiology; Microbiology

DOI:  https://doi.org/10.1016/j.isci.2023.106190
Front Cell Infect Microbiol. 2023 ;13 1137275

Lactobacillus for the treatment and prevention of atopic dermatitis: Clinical and experimental evidence.

Anni Xie, Ailing Chen, Yuqing Chen, Zichen Luo, Shanyu Jiang, Daozhen Chen, Renqiang Yu.

  Atopic dermatitis (AD) is a chronic inflammatory skin disease, accompanied by itching and swelling. The main pathological mechanism of AD is related to the imbalance between Type 2 helper cells (Th2 cells) and Type 1 helper cells (Th1 cells). Currently, no safe and effective means to treat and prevent AD are available; moreover, some treatments have side effects. Probiotics, such as some strains of Lactobacillus, can address these concerns via various pathways: i) facilitating high patient compliance; ii) regulating Th1/Th2 balance, increasing IL-10 secretion, and reducing inflammatory cytokines; iii) accelerating the maturation of the immune system, maintaining intestinal homeostasis, and improving gut microbiota; and iv) improving the symptoms of AD. This review describes the treatment and prevention of AD using 13 species of Lactobacillus. AD is commonly observed in children. Therefore, the review includes a higher proportion of studies on AD in children and fewer in adolescents and adults. However, there are also some strains that do not improve the symptoms of AD and even worsen allergies in children. In addition, a subset of the genus Lactobacillus that can prevent and relieve AD has been identified in vitro. Therefore, future studies should include more in vivo studies and randomized controlled clinical trials. Given the advantages and disadvantages mentioned above, further research in this area is urgently required.

Keywords:  Lactobacillus; atopic dermatitis; gut microbiota; immunomodulation; type 2 helper cells

DOI:  https://doi.org/10.3389/fcimb.2023.1137275