Mucosal Immunology最新文献

{"title":"A Trefoil factor 3-Lingo2 axis restrains proliferative expansion of type-1 T helper cells during GI nematode infection","authors":"Lucas M. Ethgen ,&nbsp;Christopher Pastore ,&nbsp;Cailu Lin ,&nbsp;Danielle R Reed ,&nbsp;Li-Yin Hung ,&nbsp;Bonnie Douglas ,&nbsp;Dominic Sinker ,&nbsp;De'Broski R. Herbert ,&nbsp;Nicole M. Belle","doi":"10.1016/j.mucimm.2024.02.003","DOIUrl":"10.1016/j.mucimm.2024.02.003","url":null,"abstract":"<div><p>Host defense at the mucosal interface requires collaborative interactions between diverse cell lineages. Epithelial cells damaged by microbial invaders release reparative proteins such as the Trefoil factor family (TFF) peptides that functionally restore barrier integrity. However, whether TFF peptides and their receptors also serve instructive roles for immune cell function during infection is incompletely understood. Here, we demonstrate that the intestinal trefoil factor, TFF3, restrains (T cell helper) T_H1 cell proliferation and promotes host-protective type 2 immunity against the gastrointestinal parasitic nematode <em>Trichuris muris</em>. Accordingly, T cell-specific deletion of the TFF3 receptor, leucine-rich repeat and immunoglobulin containing nogo receptor 2 (LINGO2), impairs T_H2 cell commitment, allows proliferative expansion of interferon (IFN)g⁺ cluster of differentiation (CD)4⁺ T_H1 cells and blocks normal worm expulsion through an IFNg-dependent mechanism. This study indicates that TFF3, in addition to its known tissue reparative functions, drives anti-helminth immunity by controlling the balance between T_H1/T_H2 subsets.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 238-256"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000072/pdfft?md5=b55060312fc328b7840367c8f5b26dcd&pid=1-s2.0-S1933021924000072-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139712647","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deficiency of immunoglobulin IgSF6 enhances antibacterial effects by promoting endoplasmic reticulum stress and the inflammatory response in intestinal macrophages","authors":"Yuting Wu ,&nbsp;Panrui Zhang ,&nbsp;Tianlu Shi ,&nbsp;Dan Cao ,&nbsp;Wen Pan","doi":"10.1016/j.mucimm.2024.02.006","DOIUrl":"10.1016/j.mucimm.2024.02.006","url":null,"abstract":"<div><p>Immunoglobulin superfamily (IgSF) members are known for their role as glycoproteins expressed on the surface of immune cells, enabling protein-protein interactions to sense external signals during immune responses. However, the functions of immunoglobulins localized within subcellular compartments have been less explored. In this study, we identified an endoplasmic reticulum (ER)-localized immunoglobulin, IgSF member 6 (IgSF6), that regulates ER stress and the inflammatory response in intestinal macrophages. <em>Igsf6</em> expression is sustained by microbiota and significantly upregulated upon bacterial infection. Mice lacking <em>Igsf6</em> displayed resistance to <em>Salmonella typhimurium</em> challenge but increased susceptibility to dextran sulfate sodium-induced colitis. Mechanistically, deficiency of <em>Igsf6</em> enhanced inositol-requiring enzyme 1α/-X-box binding protein 1 pathway, inflammatory response, and reactive oxygen species production leading to increased bactericidal activity of intestinal macrophages. Inhibition of reactive oxygen species or inositol-requiring enzyme 1α-X-box binding protein 1 pathway reduced the advantage of <em>Igsf6</em> deficiency in bactericidal capacity. Together, our findings provide insight into the role of IgSF6 in intestinal macrophages that modulate the ER stress response and maintain intestinal homeostasis.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 288-302"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000151/pdfft?md5=e4dc93d456f5fc73f0fc46f9e0a6c30d&pid=1-s2.0-S1933021924000151-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139932039","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TRPV1+ sensory nerves suppress conjunctival inflammation via SST-SSTR5 signaling in murine allergic conjunctivitis","authors":"Ruoxun Yu ,&nbsp;Sijing Liu ,&nbsp;Yan Li ,&nbsp;Liyuan Lu ,&nbsp;Shuoya Huang ,&nbsp;Xinwei Chen ,&nbsp;Yunxia Xue ,&nbsp;Ting Fu ,&nbsp;Jun Liu ,&nbsp;Zhijie Li","doi":"10.1016/j.mucimm.2024.02.001","DOIUrl":"10.1016/j.mucimm.2024.02.001","url":null,"abstract":"<div><p>Allergic conjunctivitis (AC), an allergen-induced ocular inflammatory disease, primarily involves mast cells (MCs) and eosinophils. The role of neuroimmune mechanisms in AC, however, remains to be elucidated. We investigated the effects of transient receptor potential vanilloid 1 (TRPV1)-positive sensory nerve ablation (using resiniferatoxin) and TRPV1 blockade (using Acetamide, N-[4-[[6-[4-(trifluoromethyl)phenyl]-4-pyrimidinyl]oxy]-2-benzothiazolyl] (AMG-517)) on ovalbumin-induced conjunctival allergic inflammation in mice. The results showed an exacerbation of allergic inflammation as evidenced by increased inflammatory gene expression, MC degranulation, tumor necrosis factor-α production by MCs, eosinophil infiltration and activation, and C-C motif chemokine 11 (CCL11) (eotaxin-1) expression in fibroblasts. Subsequent findings demonstrated that TRPV1⁺ sensory nerves secrete somatostatin (SST), which binds to SST receptor 5 (SSTR5) on MCs and conjunctival fibroblasts. SST effectively inhibited tumor necrosis factor-α production in MCs and CCL11 expression in fibroblasts, thereby reducing eosinophil infiltration and alleviating AC symptoms, including eyelid swelling, lacrimation, conjunctival chemosis, and redness. These findings suggest that targeting TRPV1⁺ sensory nerve-mediated SST-SSTR5 signaling could be a promising therapeutic strategy for AC, offering insights into neuroimmune mechanisms and potential targeted treatments.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 211-225"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000060/pdfft?md5=1900996c48b6af9ced6038dc60fe0faa&pid=1-s2.0-S1933021924000060-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139707279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immunity to pathogenic mucosal C. albicans infections mediated by oral megakaryocytes activated by IL-17 and candidalysin","authors":"Dylan Launder ,&nbsp;John T. Dillon ,&nbsp;Leah M. Wuescher ,&nbsp;Trevor Glanz ,&nbsp;Nora Abdul-Aziz ,&nbsp;Elise Mein-Chiain Yi ,&nbsp;Julian R. Naglik ,&nbsp;Randall G. Worth ,&nbsp;Heather R. Conti","doi":"10.1016/j.mucimm.2024.01.003","DOIUrl":"10.1016/j.mucimm.2024.01.003","url":null,"abstract":"<div><p>The fungus <em>Candida albicans</em> can cause mucosal infections including oropharyngeal candidiasis (OPC) in immunocompromised patients. In humans, an increased risk of fungal infections correlates with thrombocytopenia. However, our understanding of platelets and megakaryocytes (Mks) in mucosal fungal infections is almost entirely unknown. When megakaryocyte- and platelet-depleted mice were infected with OPC, the tongue showed higher fungal burden, due to decreased neutrophil accumulation. Protection depended on a distinct population of oral-resident Mks. Interleukin-17, important in antifungal immunity, was required since mice lacking the IL-17 receptor had decreased circulating platelets and their oral Mks did not expand during OPC. The secretion of the peptide toxin candidalysin activated human Mks to release platelets with antifungal capacity. Infection with a candidalysin-deficient strain resulted in decreased expansion of tongue Mks during OPC. This is the first time that a distinct megakaryocyte population was identified in the oral mucosa which is critical for immunity against fungal infection.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 182-200"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000035/pdfft?md5=d3d57914f1b6cac4d7cbdccb57d7d8b8&pid=1-s2.0-S1933021924000035-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139513250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comparison of Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic humoral immunity","authors":"Sabryna Nantel ,&nbsp;Salma Sheikh-Mohamed ,&nbsp;Gary Y.C. Chao ,&nbsp;Alexandra Kurtesi ,&nbsp;Queenie Hu ,&nbsp;Heidi Wood ,&nbsp;Karen Colwill ,&nbsp;Zhijie Li ,&nbsp;Ying Liu ,&nbsp;Laurie Seifried ,&nbsp;Benoîte Bourdin ,&nbsp;Allison McGeer ,&nbsp;William R. Hardy ,&nbsp;Olga L. Rojas ,&nbsp;Tho-Alfakar Al-Aubodah ,&nbsp;Zhiyang Liu ,&nbsp;Mario A. Ostrowski ,&nbsp;Mark A. Brockman ,&nbsp;Ciriaco A. Piccirillo ,&nbsp;Caroline Quach ,&nbsp;Jennifer L. Gommerman","doi":"10.1016/j.mucimm.2024.01.004","DOIUrl":"10.1016/j.mucimm.2024.01.004","url":null,"abstract":"<div><p>Our understanding of the quality of cellular and humoral immunity conferred by COVID-19 vaccination alone versus vaccination plus SARS-CoV-2 breakthrough (BT) infection remains incomplete. While the current (2023) SARS-CoV-2 immune landscape of Canadians is complex, in late 2021 most Canadians had either just received a third dose of COVID-19 vaccine, or had received their two-dose primary series and then experienced an Omicron BT. Herein we took advantage of this coincident timing to contrast cellular and humoral immunity conferred by three doses of vaccine versus two doses plus BT. Our results show thatBT infection induces cell-mediated immune responses to variants comparable to an intramuscular vaccine booster dose. In contrast, BT subjects had higher salivary immunoglobulin (Ig)G and IgA levels against the Omicron spike and enhanced reactivity to the ancestral spike for the IgA isotype, which also reacted with SARS-CoV-1. Serumneutralizing antibody levels against the ancestral strain and the variants were also higher after BT infection. Our results support the need for the development of intranasal vaccines that could emulate the enhanced mucosal and humoral immunity induced by Omicron BT without exposing individuals to the risks associated with SARS-CoV-2 infection.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 201-210"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000047/pdfft?md5=2d844e1ed81ce93c27def9b02d042c8e&pid=1-s2.0-S1933021924000047-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139567307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Human alveolar lining fluid from the elderly promotes Mycobacterium tuberculosis intracellular growth and translocation into the cytosol of alveolar epithelial cells","authors":"Angélica M. Olmo-Fontánez ,&nbsp;Julia M. Scordo ,&nbsp;Alyssa Schami ,&nbsp;Andreu Garcia-Vilanova ,&nbsp;Paula A. Pino ,&nbsp;Amberlee Hicks ,&nbsp;Richa Mishra ,&nbsp;Diego Jose Maselli ,&nbsp;Jay I. Peters ,&nbsp;Blanca I. Restrepo ,&nbsp;Kievershen Nargan ,&nbsp;Threnesan Naidoo ,&nbsp;Daniel L. Clemens ,&nbsp;Adrie J.C. Steyn ,&nbsp;Vivek V. Thacker ,&nbsp;Joanne Turner ,&nbsp;Larry S. Schlesinger ,&nbsp;Jordi B. Torrelles","doi":"10.1016/j.mucimm.2024.01.001","DOIUrl":"10.1016/j.mucimm.2024.01.001","url":null,"abstract":"<div><p>The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen <em>Mycobacterium tuberculosis</em> (<em>M.tb</em>) that kills one person every 18 seconds. Once <em>M.tb</em> reaches the alveolar space, it contacts alveolar lining fluid (ALF), which dictates host-cell interactions. We previously determined that age-associated dysfunction of soluble innate components in human ALF leads to accelerated <em>M.tb</em> growth within human alveolar macrophages. Here we determined the impact of human ALF on <em>M.tb</em> infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed <em>M.tb</em> had significantly increased intracellular growth with rapid replication in ATs compared to adult ALF (A-ALF)-exposed bacteria, as well as a dampened inflammatory response. A potential mechanism underlying this accelerated growth in ATs was our observation of increased bacterial translocation into the cytosol, a compartment that favors bacterial replication. These findings in the context of our previous studies highlight how the oxidative and dysfunctional status of the elderly lung mucosa determines susceptibility to <em>M.tb</em> infection, including dampening immune responses and favoring bacterial replication within alveolar resident cell populations, including ATs, the most abundant resident cell type within the alveoli.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 155-168"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000011/pdfft?md5=4e3b7413de6752a7043b6414fc657de4&pid=1-s2.0-S1933021924000011-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139377998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epithelial regulation of microbiota-immune cell dynamics","authors":"Bailey J. Didriksen ,&nbsp;Emily M. Eshleman ,&nbsp;Theresa Alenghat","doi":"10.1016/j.mucimm.2024.02.008","DOIUrl":"10.1016/j.mucimm.2024.02.008","url":null,"abstract":"<div><p>The mammalian gastrointestinal tract hosts a diverse community of trillions of microorganisms, collectively termed the microbiota, which play a fundamental role in regulating tissue physiology and immunity. Recent studies have sought to dissect the cellular and molecular mechanisms mediating communication between the microbiota and host immune system. Epithelial cells line the intestine and form an initial barrier separating the microbiota from underlying immune cells, and disruption of epithelial function has been associated with various conditions ranging from infection to inflammatory bowel diseases and cancer. From several studies, it is now clear that epithelial cells integrate signals from commensal microbes. Importantly, these non-hematopoietic cells also direct regulatory mechanisms that instruct the recruitment and function of microbiota-sensitive immune cells. In this review, we discuss the central role that has emerged for epithelial cells in orchestrating intestinal immunity and highlight epithelial pathways through which the microbiota can calibrate tissue-intrinsic immune responses.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 2","pages":"Pages 303-313"},"PeriodicalIF":8.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021924000175/pdfft?md5=5b97c1469385bb58e31660de89be93ec&pid=1-s2.0-S1933021924000175-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation","authors":"Iana Gadjalova ,&nbsp;Julia M. Heinze ,&nbsp;Marie C. Goess ,&nbsp;Julian Hofmann ,&nbsp;Annalisa Buck ,&nbsp;Marie-Christin Weber ,&nbsp;Birgit Blissenbach ,&nbsp;Maximilian Kampick ,&nbsp;Oleg Krut ,&nbsp;Katja Steiger ,&nbsp;Klaus-Peter Janssen ,&nbsp;Philipp-Alexander Neumann ,&nbsp;Jürgen Ruland ,&nbsp;Selina J. Keppler","doi":"10.1016/j.mucimm.2023.10.005","DOIUrl":"10.1016/j.mucimm.2023.10.005","url":null,"abstract":"<div><p>Dysregulated B cell responses have been described in inflammatory bowel disease (IBD) patients; however, the role of B cells in IBD pathology remained incompletely understood. We here provide evidence for the detrimental role of activated B cells during the onset of autoimmune intestinal inflammation. Using Wiskott-Aldrich Syndrome interacting protein deficient (<em>Wipf1^−/−</em>) mice as a mouse model of chronic colitis, we identified clusters of differentiation (CD)86 expression on activated B cells as a crucial factor exacerbating pro-inflammatory cytokine production of intestinal CD4 T cells. Depleting B cells through anti-CD20 antibody treatment or blocking costimulatory signals mediated by CD86 through cytotoxic T lymphocyte antigen-4-immunoglobulin (CTLA-4-Ig) diminished intestinal inflammation in our mouse model of chronic IBD at the onset of disease. This was due to a reduction in aberrant humoral immune responses and reduced CD4 T cell pro-inflammatory cytokine production, especially interferon-g (IFN-g) and granulocyte-macrophage colony-stimulating factor (GM-CSF). Interestingly, in addition to B cells isolated from the inflamed colon of <em>Wipf1^−/−</em> mice, we also found CD86 mRNA and protein expression upregulated on activated B cells isolated from inflamed tissue of human patients with IBD. B cell activation and CD86 expression were boosted by soluble CD40L <em>in vitro</em>, which we found in the serum of mice and human patients with IBD. In summary, our data provides detailed insight into the contribution of B cells to intestinal inflammation, with implications for the treatment of IBD.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 67-80"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000831/pdfft?md5=2d2ffd7849efd52bf2ca47bc577f7a92&pid=1-s2.0-S1933021923000831-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71425174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role reversals: non-canonical roles for immune and non-immune cells in the gut","authors":"Jacqueline L.E. Tearle ,&nbsp;Adelynn Tang ,&nbsp;Ajithkumar Vasanthakumar ,&nbsp;Kylie R. James","doi":"10.1016/j.mucimm.2023.11.004","DOIUrl":"10.1016/j.mucimm.2023.11.004","url":null,"abstract":"<div><p>The intestine is home to an intertwined network of epithelial, immune, and neuronal cells as well as the microbiome, with implications for immunity, systemic metabolism, and behavior. While the complexity of this microenvironment has long since been acknowledged, recent technological advances have propelled our understanding to an unprecedented level. Notably, the microbiota and non-immune or structural cells have emerged as important conductors of intestinal immunity, and by contrast, cells of both the innate and adaptive immune systems have demonstrated non-canonical roles in tissue repair and metabolism. This review highlights recent works in the following two streams: non-immune cells of the intestine performing immunological functions; and traditional immune cells exhibiting non-immune functions in the gut.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 137-146"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000879/pdfft?md5=859ac08b7373a364bc5bb7ba0a49b0fe&pid=1-s2.0-S1933021923000879-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"134647906","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A pro-inflammatory gut mucosal cytokine response is associated with mild COVID-19 disease and superior induction of serum antibodies","authors":"Dana Costigan ,&nbsp;Joe Fenn ,&nbsp;Sandi Yen ,&nbsp;Nicholas Ilott ,&nbsp;Samuel Bullers ,&nbsp;Jessica Hale ,&nbsp;William Greenhalf ,&nbsp;Emily Conibear ,&nbsp;Aleksandra Koycheva ,&nbsp;Kieran Madon ,&nbsp;Ishrat Jahan ,&nbsp;Ming Huang ,&nbsp;Anjna Badhan ,&nbsp;Eleanor Parker ,&nbsp;Carolina Rosadas ,&nbsp;Kelsey Jones ,&nbsp;Myra McClure ,&nbsp;Richard Tedder ,&nbsp;Graham Taylor ,&nbsp;Kenneth J. Baillie ,&nbsp;Emily E. Thornton","doi":"10.1016/j.mucimm.2023.11.005","DOIUrl":"10.1016/j.mucimm.2023.11.005","url":null,"abstract":"<div><p>The relationship between gastrointestinal tract infection, the host immune response, and the clinical outcome of disease is not well understood in COVID-19. We sought to understand the effect of intestinal immune responses to SARS-CoV-2 on patient outcomes including the magnitude of systemic antibody induction. Combining two prospective cohort studies, International Severe Acute Respiratory and emerging Infections Consortium Comprehensive Clinical Characterisations Collaboration (ISARIC4C) and Integrated Network for Surveillance, Trials and Investigations into COVID-19 Transmission (INSTINCT), we acquired samples from 88 COVID-19 cases representing the full spectrum of disease severity and analysed viral RNA and host gut cytokine responses in the context of clinical and virological outcome measures. There was no correlation between the upper respiratory tract and faecal viral loads. Using hierarchical clustering, we identified a group of fecal cytokines including Interleukin-17A, Granulocyte macrophage colony-stimulating factor, Tumor necrosis factorα, Interleukin-23, and S100A8, that were transiently elevated in mild cases and also correlated with the magnitude of systemic anti-Spike-receptor-binding domain antibody induction. Receiver operating characteristic curve analysis showed that expression of these gut cytokines at study enrolment in hospitalised COVID-19 cases was associated negatively with overall clinical severity implicating a protective role in COVID-19. This suggests that a productive intestinal immune response may be beneficial in the response to a respiratory pathogen and a biomarker of a successful barrier response.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 111-123"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000880/pdfft?md5=df21bbfa62f12cf77ac765711bf3a967&pid=1-s2.0-S1933021923000880-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138299580","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}