bims-bac4me Biomed News
on Microbiome and trained immunity
Issue of 2024‒06‒09
24 papers selected by
Chun-Chi Chang, University Hospital Zurich
  1. Multifaceted roles of trained immunity in diverse pathological contexts.
  2. Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues.
  3. Macrophage fate: to kill or not to kill?
  4. Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages.
  5. Well-controlled mucosal exudation of plasma proteins in airways with intact and regenerating epithelium.
  6. Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells.
  7. Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.
  8. Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi.
  9. Deficiency in non-classical major histocompatibility class II-like molecule, H2-O confers protection against Staphylococcus aureus in mice.
  10. Past, present, and future of microbiome-based therapies.
  11. ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.
  12. Unraveling host regulation of gut microbiota through the epigenome-microbiome axis.
  13. Staphylococcus aureus: No ticket for the Paris 2024 Olympic Games!
  14. Gut microbes coordinate pulmonary immunity.
  15. Orchestration of macrophage polarization dynamics by fibroblast-secreted exosomes during skin wound healing.
  16. Cell-wall-anchored proteins affect invasive host colonization and biofilm formation in Staphylococcus aureus.
  17. Cell Culture Differentiation and Proliferation Conditions Influence the In Vitro Regeneration of the Human Airway Epithelium.
  18. Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis.
  19. Cooperative growth in microbial communities is a driver of multistability.
  20. A simple rule for predicting function of microbial communities.
  21. Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?
  22. Microbiome-Based Diagnostics for Disease: Where Are We Now and Where Are We Headed?
  23. Epithelial hypoxia maintains colonization resistance against Candida albicans.
  24. Unifying the airway through multiomics.
  1. BMB Rep. 2024 Jun 05. pii: 6218. [Epub ahead of print]
    Multifaceted roles of trained immunity in diverse pathological contexts.
    Hyo Jin Park, Su Min Kim, Un Yung Choi, Lark Kyun Kim.
      Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as β-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications.
  2. Front Immunol. 2024 ;15 1395786
    Lactate and lactylation in macrophage metabolic reprogramming: current progress and outstanding issues.
    Bangjun Xu, Yi Liu, Ning Li, Qing Geng.
      It is commonly known that different macrophage phenotypes play specific roles in different pathophysiological processes. In recent years, many studies have linked the phenotypes of macrophages to their characteristics in different metabolic pathways, suggesting that macrophages can perform different functions through metabolic reprogramming. It is now gradually recognized that lactate, previously overlooked as a byproduct of glycolytic metabolism, acts as a signaling molecule in regulating multiple biological processes, including immunological responses and metabolism. Recently, lactate has been found to mediate epigenetic changes in macrophages through a newfound lactylation modification, thereby regulating their phenotypic transformation. This novel finding highlights the significant role of lactate metabolism in macrophage function. In this review, we summarize the features of relevant metabolic reprogramming in macrophages and the role of lactate metabolism therein. We also review the progress of research on the regulation of macrophage metabolic reprogramming by lactylation through epigenetic mechanisms.
    Keywords:  Post-translational modification (PTM); lactate; lactylation; macrophage; metabolic reprogramming
    DOI:  https://doi.org/10.3389/fimmu.2024.1395786
  3. Infect Immun. 2024 Jun 03. e0047623
    Macrophage fate: to kill or not to kill?
    Armando M Marrufo, Ana Lidia Flores-Mireles.
      Macrophages are dynamic innate immune cells that either reside in tissue, serving as sentinels, or recruited as monocytes from bone marrow into inflamed and infected tissue. In response to cues in the tissue microenvironment (TME), macrophages polarize on a continuum toward M1 or M2 with diverse roles in progression and resolution of disease. M1-like macrophages exhibit proinflammatory functions with antimicrobial and anti-tumorigenic activities, while M2-like macrophages have anti-inflammatory functions that generally resolve inflammatory responses and orchestrate a tissue healing process. Given these opposite phenotypes, proper spatiotemporal coordination of macrophage polarization in response to cues within the TME is critical to effectively resolve infectious disease and regulate wound healing. However, if this spatiotemporal coordination becomes disrupted due to persistent infection or dysregulated coagulation, macrophages' inappropriate response to these cues will result in the development of diseases with clinically unfavorable outcomes. Since plasticity and heterogeneity are hallmarks of macrophages, they are attractive targets for therapies to reprogram toward specific phenotypes that could resolve disease and favor clinical prognosis. In this review, we discuss how basic science studies have elucidated macrophage polarization mechanisms in TMEs during infections and inflammation, particularly coagulation. Therefore, understanding the dynamics of macrophage polarization within TMEs in diseases is important in further development of targeted therapies.
    Keywords:  M1; M1/M2; M2; coagulation; innate immunity; macrophage polarization; macrophages; tissue microenvironment
    DOI:  https://doi.org/10.1128/iai.00476-23
  4. bioRxiv. 2024 May 26. pii: 2024.05.22.594428. [Epub ahead of print]
    Absence of c-Maf and IL-10 enables Type I IFN enhancement of innate responses to low-dose LPS in alveolar macrophages.
    Pamelia N Lim, Maritza M Cervantes, Linh K Pham, Sydney Doherty, Ankita Tufts, Divya Dubey, Dat Mai, Alan Aderem, Alan H Diercks, Alissa C Rothchild.
      Alveolar macrophages (AMs) are lower-airway resident myeloid cells and are among the first to respond to inhaled pathogens. Here, we interrogate AM innate sensing to Pathogen Associated Molecular Patterns (PAMPs) and determine AMs have decreased responses to low- dose LPS compared to other macrophages, as measured by TNF, IL-6, Ifnb , and Ifit3 . We find the reduced response to low-dose LPS correlates with minimal TLR4 and CD14 surface expression, despite sufficient internal expression of TLR4. Additionally, we find that AMs do not produce IL-10 in response to a variety of PAMPs due to low expression of transcription factor c- Maf and that lack of IL-10 production contributes to an enhancement of pro-inflammatory responses by Type I IFN. Our findings demonstrate that AMs have cell-intrinsic dampened responses to LPS, which is enhanced by type I IFN exposure. These data implicate conditions where AMs may have reduced or enhanced sentinel responses to bacterial infections.HIGHLIGHTS: Alveolar macrophages (AMs) do not produce TNF or IL-6 in response to low-dose LPS due to minimal surface expression of TLR4 and CD14Lack of AM IL-10 production is dependent on low c-Maf expressionExogenous c-Maf expression increases AM IL-10 productionIFNβ enhances AM TNF and IL-6 responses to low-dose LPS and this is dependent on a lack of IL-10.
    DOI:  https://doi.org/10.1101/2024.05.22.594428
  5. Physiol Rep. 2024 Jun;12(11): e16096
    Well-controlled mucosal exudation of plasma proteins in airways with intact and regenerating epithelium.
    Carl Persson.
      Superficial, systemic microcirculations, distinct from the pulmonary circulation, supply the mucosae of human nasal and conducting airways. Non-injurious, inflammatory challenges of the airway mucosa cause extravasation without overt mucosal oedema. Instead, likely reflecting minimal increases in basolateral hydrostatic pressure, circulating proteins/peptides of all sizes are transmitted paracellularly across the juxtaposed epithelial barrier. Thus, small volumes of extravasated, unfiltered bulk plasma appear on the mucosal surface at nasal and bronchial sites of challenge. Importantly, the plasma-exuding mucosa maintains barrier integrity against penetrability of inhaled molecules. Thus, one-way epithelial penetrability, strict localization, and well-controlled magnitude and duration are basic characteristics of the plasma exudation response in human intact airways. In vivo experiments in human-like airways demonstrate that local plasma exudation is also induced by non-sanguineous removal of epithelium over an intact basement membrane. This humoral response results in a protective, repair-promoting barrier kept together by a fibrin-fibronectin net. Plasma exudation stops once the provisional barrier is substituted by a new cellular cover consisting of speedily migrating repair cells, which may emanate from all types of epithelial cells bordering the denuded patch. Exuded plasma on the surface of human airways reflects physiological microvascular-epithelial cooperation in first line mucosal defense at sites of intact and regenerating epithelium.
    Keywords:  epithelial regeneration; first line defense; human airway mucosa; maintained epithelial barrier; microvascular‐epithelial cooperation; plasma exudation
    DOI:  https://doi.org/10.14814/phy2.16096
  6. Sci Immunol. 2024 Jun 07. 9(96): eadl2388
    Plasma membrane abundance dictates phagocytic capacity and functional cross-talk in myeloid cells.
    Benjamin Y Winer, Alexander H Settle, Alexandrina M Yakimov, Carlos Jeronimo, Tomi Lazarov, Murray Tipping, Michelle Saoi, Anjelique Sawh, Anna-Liisa L Sepp, Michael Galiano, Justin S A Perry, Yung Yu Wong, Frederic Geissmann, Justin Cross, Ting Zhou, Lance C Kam, H Amalia Pasolli, Tobias Hohl, Jason G Cyster, Orion D Weiner, Morgan Huse.
      Professional phagocytes like neutrophils and macrophages tightly control what they consume, how much they consume, and when they move after cargo uptake. We show that plasma membrane abundance is a key arbiter of these cellular behaviors. Neutrophils and macrophages lacking the G protein subunit Gβ4 exhibited profound plasma membrane expansion, accompanied by marked reduction in plasma membrane tension. These biophysical changes promoted the phagocytosis of bacteria, fungus, apoptotic corpses, and cancer cells. We also found that Gβ4-deficient neutrophils are defective in the normal inhibition of migration following cargo uptake. Sphingolipid synthesis played a central role in these phenotypes by driving plasma membrane accumulation in cells lacking Gβ4. In Gβ4 knockout mice, neutrophils not only exhibited enhanced phagocytosis of inhaled fungal conidia in the lung but also increased trafficking of engulfed pathogens to other organs. Together, these results reveal an unexpected, biophysical control mechanism central to myeloid functional decision-making.
    DOI:  https://doi.org/10.1126/sciimmunol.adl2388
  7. Nat Commun. 2024 Jun 03. 15(1): 4708
    Longitudinal multicompartment characterization of host-microbiota interactions in patients with acute respiratory failure.
    Georgios D Kitsios, Khaled Sayed, Adam Fitch, Haopu Yang, Noel Britton, Faraaz Shah, William Bain, John W Evankovich, Shulin Qin, Xiaohong Wang, Kelvin Li, Asha Patel, Yingze Zhang, Josiah Radder, Charles Dela Cruz, Daniel A Okin, Ching-Ying Huang, Daria Van Tyne, Panayiotis V Benos, Barbara Methé, Peggy Lai, Alison Morris, Bryan J McVerry.
      Critical illness can significantly alter the composition and function of the human microbiome, but few studies have examined these changes over time. Here, we conduct a comprehensive analysis of the oral, lung, and gut microbiota in 479 mechanically ventilated patients (223 females, 256 males) with acute respiratory failure. We use advanced DNA sequencing technologies, including Illumina amplicon sequencing (utilizing 16S and ITS rRNA genes for bacteria and fungi, respectively, in all sample types) and Nanopore metagenomics for lung microbiota. Our results reveal a progressive dysbiosis in all three body compartments, characterized by a reduction in microbial diversity, a decrease in beneficial anaerobes, and an increase in pathogens. We find that clinical factors, such as chronic obstructive pulmonary disease, immunosuppression, and antibiotic exposure, are associated with specific patterns of dysbiosis. Interestingly, unsupervised clustering of lung microbiota diversity and composition by 16S independently predicted survival and performed better than traditional clinical and host-response predictors. These observations are validated in two separate cohorts of COVID-19 patients, highlighting the potential of lung microbiota as valuable prognostic biomarkers in critical care. Understanding these microbiome changes during critical illness points to new opportunities for microbiota-targeted precision medicine interventions.
    DOI:  https://doi.org/10.1038/s41467-024-48819-8
  8. Sci Rep. 2024 06 04. 14(1): 12811
    Transcriptional profiling links unique human macrophage phenotypes to the growth of intracellular Salmonella enterica serovar Typhi.
    Ruth Schade, Daniel S C Butler, Joy A McKenna, Blanda Di Luccia, Vida Shokoohi, Meagan Hamblin, Trung H M Pham, Denise M Monack.
      Macrophages provide a crucial environment for Salmonella enterica serovar Typhi (S. Typhi) to multiply during typhoid fever, yet our understanding of how human macrophages and S. Typhi interact remains limited. In this study, we delve into the dynamics of S. Typhi replication within human macrophages and the resulting heterogeneous transcriptomic responses of macrophages during infection. Our study reveals key factors that influence macrophage diversity, uncovering distinct immune and metabolic pathways associated with different stages of S. Typhi intracellular replication in macrophages. Of note, we found that macrophages harboring replicating S. Typhi are skewed towards an M1 pro-inflammatory state, whereas macrophages containing non-replicating S. Typhi exhibit neither a distinct M1 pro-inflammatory nor M2 anti-inflammatory state. Additionally, macrophages with replicating S. Typhi were characterized by the increased expression of genes associated with STAT3 phosphorylation and the activation of the STAT3 transcription factor. Our results shed light on transcriptomic pathways involved in the susceptibility of human macrophages to intracellular S. Typhi replication, thereby providing crucial insight into host phenotypes that restrict and support S. Typhi infection.
    DOI:  https://doi.org/10.1038/s41598-024-63588-6
  9. PLoS Pathog. 2024 Jun 06. 20(6): e1012306
    Deficiency in non-classical major histocompatibility class II-like molecule, H2-O confers protection against Staphylococcus aureus in mice.
    Emily Cullum, Yunys Perez-Betancourt, Miaomiao Shi, Eirinaios Gkika, Olaf Schneewind, Dominique Missiakas, Tatyana Golovkina.
      Staphylococcus aureus is a human-adapted pathogen that replicates by asymptomatically colonizing its host. S. aureus is also the causative agent of purulent skin and soft tissue infections as well as bloodstream infections that result in the metastatic seeding of abscess lesions in all organ tissues. Prolonged colonization, infection, disease relapse, and recurrence point to the versatile capacity of S. aureus to bypass innate and adaptive immune defenses as well as the notion that some hosts fail to generate protective immune responses. Here, we find a genetic trait that provides protection against this pathogen. Mice lacking functional H2-O, the equivalent of human HLA-DO, inoculated with a mouse-adapted strain of S. aureus, efficiently decolonize the pathogen. Further, these decolonized animals resist subsequent bloodstream challenge with methicillin-resistant S. aureus. A genetic approach demonstrates that T-cell dependent B cell responses are required to control S. aureus colonization and infection in H2-O-deficient mice. Reduced bacterial burdens in these animals correlate with increased titers and enhanced phagocytic activity of S. aureus-specific antibodies. H2-O negatively regulates the loading of high affinity peptides on major histocompatibility class II (MHC-II) molecules. Thus, we hypothesize that immune responses against S. aureus are derepressed in mice lacking H2-O because more high affinity peptides are presented by MHC-II. We speculate that loss-of-function HLA-DO alleles may similarly control S. aureus replication in humans.
    DOI:  https://doi.org/10.1371/journal.ppat.1012306
  10. Microbiome Res Rep. 2024 ;3(2): 23
    Past, present, and future of microbiome-based therapies.
    Pilar Manrique, Ignacio Montero, Marta Fernandez-Gosende, Noelia Martinez, Claudio Hidalgo Cantabrana, David Rios-Covian.
      Technological advances in studying the human microbiome in depth have enabled the identification of microbial signatures associated with health and disease. This confirms the crucial role of microbiota in maintaining homeostasis and the host health status. Nowadays, there are several ways to modulate the microbiota composition to effectively improve host health; therefore, the development of therapeutic treatments based on the gut microbiota is experiencing rapid growth. In this review, we summarize the influence of the gut microbiota on the development of infectious disease and cancer, which are two of the main targets of microbiome-based therapies currently being developed. We analyze the two-way interaction between the gut microbiota and traditional drugs in order to emphasize the influence of gut microbial composition on drug effectivity and treatment response. We explore the different strategies currently available for modulating this ecosystem to our benefit, ranging from 1st generation intervention strategies to more complex 2nd generation microbiome-based therapies and their regulatory framework. Lastly, we finish with a quick overview of what we believe is the future of these strategies, that is 3rd generation microbiome-based therapies developed with the use of artificial intelligence (AI) algorithms.
    Keywords:  LBP; MBP; Microbiome-based therapies; biological drugs; microbiota
    DOI:  https://doi.org/10.20517/mrr.2023.80
  11. Nat Rev Microbiol. 2024 Jun 03.
    ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.
    William R Miller, Cesar A Arias.
      The rise of antibiotic resistance and a dwindling antimicrobial pipeline have been recognized as emerging threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria for which effective therapies were rapidly needed. Now, entering the third decade of the twenty-first century, and despite the introduction of several new antibiotics and antibiotic adjuvants, such as novel β-lactamase inhibitors, these organisms continue to represent major therapeutic challenges. These bacteria share several key biological features, including adaptations for survival in the modern health-care setting, diverse methods for acquiring resistance determinants and the dissemination of successful high-risk clones around the world. With the advent of next-generation sequencing, novel tools to track and combat the spread of these organisms have rapidly evolved, as well as renewed interest in non-traditional antibiotic approaches. In this Review, we explore the current epidemiology and clinical impact of this important group of bacterial pathogens and discuss relevant mechanisms of resistance to recently introduced antibiotics that affect their use in clinical settings. Furthermore, we discuss emerging therapeutic strategies needed for effective patient care in the era of widespread antimicrobial resistance.
    DOI:  https://doi.org/10.1038/s41579-024-01054-w
  12. Trends Microbiol. 2024 Jun 04. pii: S0966-842X(24)00137-9. [Epub ahead of print]
    Unraveling host regulation of gut microbiota through the epigenome-microbiome axis.
    Michael L Pepke, Søren B Hansen, Morten T Limborg.
      Recent studies of dynamic interactions between epigenetic modifications of a host organism and the composition or activity of its associated gut microbiota suggest an opportunity for the host to shape its microbiome through epigenetic alterations that lead to changes in gene expression and noncoding RNA activity. We use insights from microbiota-induced epigenetic changes to review the potential of the host to epigenetically regulate its gut microbiome, from which a bidirectional 'epigenome-microbiome axis' emerges. This axis embeds environmentally induced variation, which may influence the adaptive evolution of host-microbe interactions. We furthermore present our perspective on how the epigenome-microbiome axis can be understood and investigated within a holo-omic framework with potential applications in the applied health and food sciences.
    Keywords:  DNA methylation; epigenetics; histone acetylation; hologenomics; host–microbiota interaction; noncoding RNA
    DOI:  https://doi.org/10.1016/j.tim.2024.05.006
  13. Infect Dis Now. 2024 Mar 11. pii: S2666-9919(24)00037-X. [Epub ahead of print] 104882
    Staphylococcus aureus: No ticket for the Paris 2024 Olympic Games!
    Anne-Lise Maucotel, Camille Kolenda, Frédéric Laurent, Anne Tristan.
      Athletes are vulnerable to Staphylococcus aureus infections due to skin-to-skin contact and skin abrasions during training and competitions involving sharied sport equipment or toiletries, which promote the spread of the bacteria between athletes and within sport teams. This results not only in higher prevalence of S.aureus carriage among athletes compared to the general population, but also in outbreaks of infections, particularly skin infections, within sports teams. To limit the spread of S. aureus among athletes, a decolonization protocol can be applied when clustered cases of S. aureus infections occur, especially if Panton-Valentine leukocidin-producing strains are implicated. Finally, to avoid exposing athletes to S.aureus transmission/colonization, it is recommended to establish strict and clearly formulated individual and collective hygiene rules and to regularly disinfect shared sports equipment.
    Keywords:  Athletes; Infection risk; Staphylococcus aureus; Transmission
    DOI:  https://doi.org/10.1016/j.idnow.2024.104882
  14. Proc Natl Acad Sci U S A. 2024 Jun 18. 121(25): e2408800121
    Gut microbes coordinate pulmonary immunity.
    Chryso Christodoulou, Thomas B Clarke.
      
    DOI:  https://doi.org/10.1073/pnas.2408800121
  15. J Invest Dermatol. 2024 Jun 03. pii: S0022-202X(24)00445-7. [Epub ahead of print]
    Orchestration of macrophage polarization dynamics by fibroblast-secreted exosomes during skin wound healing.
    Cheng Chen, Jiacai Yang, Ruoyu Shang, Yuanyang Tang, Xin Cai, Yunxia Chen, Zhihui Liu, Wengang Hu, Weiguang Zhang, Xiaorong Zhang, Yong Huang, Xiaohong Hu, Wenjing Yin, Qudong Lu, Hao Sheng, Dejiang Fan, Zhenyu Ju, Gaoxing Luo, Weifeng He.
      Macrophages undertake pivotal yet dichotomous functions during skin wound healing, mediating both early pro-inflammatory immune activation and late anti-inflammatory tissue remodeling processes. The timely phenotypic transition of macrophages from inflammatory M1 to pro-resolving M2 activation states is essential for efficient healing. However, the endogenous mechanisms calibrating macrophage polarization in accordance with the evolving tissue milieu remain undefined. Here, we reveal an indispensable immunomodulatory role for fibroblast-secreted exosomes in directing macrophage activation dynamics. Fibroblast exosomes permitted spatiotemporal coordination of macrophage phenotypes independent of direct intercellular contact. Exosomes enhanced macrophage sensitivity to both M1 and M2 polarizing stimuli, yet also accelerated timely switching from M1 to M2 phenotypes. Exosomes inhibition dysregulated macrophage responses resulting in aberrant inflammation and impaired healing, while provision of exogenous fibroblast exosomes corrected defects. Topical application of fibroblast exosomes onto chronic diabetic wounds normalized dysregulated macrophage activation to resolve inflammation and restore productive healing. Our findings elucidate fibroblast-secreted exosomes as remote programmers of macrophage polarization that calibrate immunological transitions essential for tissue repair. Harnessing exosomes represents a previously unreported approach to steer productive macrophage activation states with immense therapeutic potential for promoting healing in chronic inflammatory disorders.
    Keywords:  exosomes; fibroblasts; macrophages; wound healing
    DOI:  https://doi.org/10.1016/j.jid.2024.05.007
  16. Microbiol Res. 2024 May 27. pii: S0944-5013(24)00183-6. [Epub ahead of print]285 127782
    Cell-wall-anchored proteins affect invasive host colonization and biofilm formation in Staphylococcus aureus.
    Zhenbo Xu, Yaqin Li, Aijuan Xu, Thanapop Soteyome, Lei Yuan, Qin Ma, Gamini Seneviratne, Xuejie Li, Junyan Liu.
      As a major human and animal pathogen, Staphylococcus aureus can attach to medical implants (abiotic surface) or host tissues (biotic surface), and further establish robust biofilms which enhances resistance and persistence to host immune system and antibiotics. Cell-wall-anchored proteins (CWAPs) covalently link to peptidoglycan, and largely facilitate the colonization of S. aureus on various surfaces (including adhesion and biofilm formation) and invasion into host cells (including adhesion, immune evasion, iron acquisition and biofilm formation). During biofilm formation, CWAPs function in adhesion, aggregation, collagen-like fiber network formation, and consortia formation. In this review, we firstly focus on the structural features of CWAPs, including their intracellular function and interactions with host cells, as well as the functions and ligand binding of CWAPs in different stages of S. aureus biofilm formation. Then, the roles of CWAPs in different biofilm processes with regards in development of therapeutic approaches are clarified, followed by the association between CWAPs genes and clonal lineages. By touching upon these aspects, we hope to provide comprehensive knowledge and clearer understanding on the CWAPs of S. aureus and their roles in biofilm formation, which may further aid in prevention and treatment infection and vaccine development.
    Keywords:  Abiotic and biotic surface; Biofilm; Cell-wall-anchored proteins; Colonization; Staphylococcus aureus
    DOI:  https://doi.org/10.1016/j.micres.2024.127782
  17. Am J Respir Cell Mol Biol. 2024 Jun 06.
    Cell Culture Differentiation and Proliferation Conditions Influence the In Vitro Regeneration of the Human Airway Epithelium.
    Elisa Redman, Morgane Fierville, Amélie Cavard, Magali Plaisant, Marie-Jeanne Arguel, Sandra Ruiz Garcia, Eamon M McAndrew, Cédric Girard-Riboulleau, Kevin Lebrigand, Virginie Magnone, Gilles Ponzio, Delphine Gras, Pascal Chanez, Sophie Abelanet, Pascal Barbry, Brice Marcet, Laure-Emmanuelle Zaragosi.
      The human airway mucociliary epithelium can be recapitulated in vitro using primary cells cultured in an Air-Liquid Interface (ALI), a reliable surrogate to perform pathophysiological studies. As tremendous variations exist between media used for ALI-cultured human airway epithelial cells, our study aimed to evaluate the impact of several media (BEGMTM, PneumaCultTM, "Half&Half" and "Clancy") on cell type distribution using single-cell RNA sequencing and imaging. Our work revealed the impact of these media on cell composition, gene expression profile, cell signaling and epithelial morphology. We found higher proportions of multiciliated cells in PneumaCultTM-ALI and Half&Half, stronger EGF signaling from basal cells in BEGMTM-ALI, differential expression of the SARS-CoV-2 entry factor ACE2, and distinct secretome transcripts depending on media used. We also established that proliferation in PneumaCultTM-Ex Plus favored secretory cell fate, showing the key influence of proliferation media on late differentiation epithelial characteristics. Altogether, our data offer a comprehensive repertoire for evaluating the effects of culture conditions on airway epithelial differentiation and will help to choose the most relevant medium according to the processes to be investigated such as cilia, mucus biology or viral infection. We detail useful parameters that should be explored to document airway epithelial cell fate and morphology.
    Keywords:  Air-Liquid Interface cell culture; airway epithelium; cell fate; culture medium; single-cell RNA sequencing
    DOI:  https://doi.org/10.1165/rcmb.2023-0356MA
  18. iScience. 2024 Jun 21. 27(6): 109993
    Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis.
    Shiloh R Lueschow-Guijosa, Amy H Stanford, Jennifer N Berger, Huiyu Gong, Timothy J Boly, Benjamin A H Jensen, Peter Nordkild, Alexandra J Leegwater, Jan Wehkamp, Mark A Underwood, Steven J McElroy.
      Necrotizing enterocolitis (NEC) is a leading cause of preterm infant morbidity and mortality. Treatment for NEC is limited and non-targeted, which makes new treatment and prevention strategies critical. Host defense peptides (HDPs) are essential components of the innate immune system and have multifactorial mechanisms in host defense. LL-37 and hBD2 are two HDPs that have been shown in prior literature to protect from neonatal sepsis-induced mortality or adult inflammatory bowel disease, respectively. Therefore, this article sought to understand if these two HDPs could influence NEC severity in murine preclinical models. NEC was induced in P14-16 C57Bl/6 mice and HDPs were provided as a pretreatment or treatment. Both LL-37 and hBD2 resulted in decreased NEC injury scores as a treatment and hBD2 as a pretreatment. Our data suggest LL-37 functions through antimicrobial properties, while hBD2 functions through decreases in inflammation and improvement of intestinal barrier integrity.
    Keywords:  Biological sciences; Immunology; Molecular biology
    DOI:  https://doi.org/10.1016/j.isci.2024.109993
  19. Nat Commun. 2024 Jun 03. 15(1): 4709
    Cooperative growth in microbial communities is a driver of multistability.
    William Lopes, Daniel R Amor, Jeff Gore.
      Microbial communities often exhibit more than one possible stable composition for the same set of external conditions. In the human microbiome, these persistent changes in species composition and abundance are associated with health and disease states, but the drivers of these alternative stable states remain unclear. Here we experimentally demonstrate that a cross-kingdom community, composed of six species relevant to the respiratory tract, displays four alternative stable states each dominated by a different species. In pairwise coculture, we observe widespread bistability among species pairs, providing a natural origin for the multistability of the full community. In contrast with the common association between bistability and antagonism, experiments reveal many positive interactions within and between community members. We find that multiple species display cooperative growth, and modeling predicts that this could drive the observed multistability within the community as well as non-canonical pairwise outcomes. A biochemical screening reveals that glutamate either reduces or eliminates cooperativity in the growth of several species, and we confirm that such supplementation reduces the extent of bistability across pairs and reduces multistability in the full community. Our findings provide a mechanistic explanation of how cooperative growth rather than competitive interactions can underlie multistability in microbial communities.
    DOI:  https://doi.org/10.1038/s41467-024-48521-9
  20. Cell. 2024 Jun 06. pii: S0092-8674(24)00450-1. [Epub ahead of print]187(12): 2905-2906
    A simple rule for predicting function of microbial communities.
    Sergey Kryazhimskiy.
      Microbial communities perform many important functions, such as carbon sequestration, decomposition, pathogen resistance, etc., but quantitatively predicting functions of new communities remains a major challenge. In this issue of Cell, Diaz-Colunga et al. report a new simple statistical regularity that enables such predictions.
    DOI:  https://doi.org/10.1016/j.cell.2024.04.024
  21. Front Immunol. 2024 ;15 1379754
    Sex-related immunity: could Toll-like receptors be the answer in acute inflammatory response?
    Alexandros Popotas, Georges Jacques Casimir, Francis Corazza, Nicolas Lefèvre.
      An increasing number of studies have highlighted the existence of a sex-specific immune response, wherein men experience a worse prognosis in cases of acute inflammatory diseases. Initially, this sex-dependent inflammatory response was attributed to the influence of sex hormones. However, a growing body of evidence has shifted the focus toward the influence of chromosomes rather than sex hormones in shaping these inflammatory sex disparities. Notably, certain pattern recognition receptors, such as Toll-like receptors (TLRs), and their associated immune pathways have been implicated in driving the sex-specific immune response. These receptors are encoded by genes located on the X chromosome. TLRs are pivotal components of the innate immune system, playing crucial roles in responding to infectious diseases, including bacterial and viral pathogens, as well as trauma-related conditions. Importantly, the TLR-mediated inflammatory responses, as indicated by the production of specific proteins and cytokines, exhibit discernible sex-dependent patterns. In this review, we delve into the subject of sex bias in TLR activation and explore its clinical implications relatively to both the X chromosome and the hormonal environment. The overarching objective is to enhance our understanding of the fundamental mechanisms underlying these sex differences.
    Keywords:  TLR-Toll-like receptor; X chromosome; hormones; infection; innate immunity; sepsis; sex; trauma
    DOI:  https://doi.org/10.3389/fimmu.2024.1379754
  22. Clin Chem. 2024 Jun 03. 70(6): 792-797
    Microbiome-Based Diagnostics for Disease: Where Are We Now and Where Are We Headed?
    Melanie L Yarbrough, Rebekah E Dumm, Lynn Bry, Brendan J Kelly, Drew Schwartz, Aayushi Uberoi.
      
    DOI:  https://doi.org/10.1093/clinchem/hvae069
  23. Cell Host Microbe. 2024 Jun 01. pii: S1931-3128(24)00180-X. [Epub ahead of print]
    Epithelial hypoxia maintains colonization resistance against Candida albicans.
    Hannah P Savage, Derek J Bays, Connor R Tiffany, Mariela A F Gonzalez, Eli J Bejarano, Thaynara P Carvalho, Zheng Luo, Hugo L P Masson, Henry Nguyen, Renato L Santos, Krystle L Reagan, George R Thompson, Andreas J Bäumler.
      Antibiotic treatment promotes the outgrowth of intestinal Candida albicans, but the mechanisms driving this fungal bloom remain incompletely understood. We identify oxygen as a resource required for post-antibiotic C. albicans expansion. C. albicans depleted simple sugars in the ceca of gnotobiotic mice but required oxygen to grow on these resources in vitro, pointing to anaerobiosis as a potential factor limiting growth in the gut. Clostridia species limit oxygen availability in the large intestine by producing butyrate, which activates peroxisome proliferator-activated receptor gamma (PPAR-γ) signaling to maintain epithelial hypoxia. Streptomycin treatment depleted Clostridia-derived butyrate to increase epithelial oxygenation, but the PPAR-γ agonist 5-aminosalicylic acid (5-ASA) functionally replaced Clostridia species to restore epithelial hypoxia and colonization resistance against C. albicans. Additionally, probiotic Escherichia coli required oxygen respiration to prevent a post-antibiotic bloom of C. albicans, further supporting the role of oxygen in colonization resistance. We conclude that limited access to oxygen maintains colonization resistance against C. albicans.
    Keywords:  Candida albicans; Clostridia; Escherichia coli; colonization resistance; epithelial hypoxia
    DOI:  https://doi.org/10.1016/j.chom.2024.05.008
  24. Ann Allergy Asthma Immunol. 2024 Jun;pii: S1081-1206(24)00172-8. [Epub ahead of print]132(6): 667-668
    Unifying the airway through multiomics.
    Ahmad R Sedaghat, Katie M Phillips.
      
    DOI:  https://doi.org/10.1016/j.anai.2024.03.018
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