Pub Date : 2024-04-01DOI: 10.1016/j.mucimm.2024.01.004
Sabryna Nantel , Salma Sheikh-Mohamed , Gary Y.C. Chao , Alexandra Kurtesi , Queenie Hu , Heidi Wood , Karen Colwill , Zhijie Li , Ying Liu , Laurie Seifried , Benoîte Bourdin , Allison McGeer , William R. Hardy , Olga L. Rojas , Tho-Alfakar Al-Aubodah , Zhiyang Liu , Mario A. Ostrowski , Mark A. Brockman , Ciriaco A. Piccirillo , Caroline Quach , Jennifer L. Gommerman
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.
{"title":"Comparison of Omicron breakthrough infection versus monovalent SARS-CoV-2 intramuscular booster reveals differences in mucosal and systemic humoral immunity","authors":"Sabryna Nantel , Salma Sheikh-Mohamed , Gary Y.C. Chao , Alexandra Kurtesi , Queenie Hu , Heidi Wood , Karen Colwill , Zhijie Li , Ying Liu , Laurie Seifried , Benoîte Bourdin , Allison McGeer , William R. Hardy , Olga L. Rojas , Tho-Alfakar Al-Aubodah , Zhiyang Liu , Mario A. Ostrowski , Mark A. Brockman , Ciriaco A. Piccirillo , Caroline Quach , 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}
Pub Date : 2024-04-01DOI: 10.1016/j.mucimm.2024.01.001
Angélica M. Olmo-Fontánez , Julia M. Scordo , Alyssa Schami , Andreu Garcia-Vilanova , Paula A. Pino , Amberlee Hicks , Richa Mishra , Diego Jose Maselli , Jay I. Peters , Blanca I. Restrepo , Kievershen Nargan , Threnesan Naidoo , Daniel L. Clemens , Adrie J.C. Steyn , Vivek V. Thacker , Joanne Turner , Larry S. Schlesinger , Jordi B. Torrelles
The elderly population is highly susceptible to developing respiratory diseases, including tuberculosis, a devastating disease caused by the airborne pathogen Mycobacterium tuberculosis (M.tb) that kills one person every 18 seconds. Once M.tb 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 M.tb growth within human alveolar macrophages. Here we determined the impact of human ALF on M.tb infection of alveolar epithelial type cells (ATs), another critical lung cellular determinant of infection. We observed that elderly ALF (E-ALF)-exposed M.tb 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 M.tb 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.
{"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 , Julia M. Scordo , Alyssa Schami , Andreu Garcia-Vilanova , Paula A. Pino , Amberlee Hicks , Richa Mishra , Diego Jose Maselli , Jay I. Peters , Blanca I. Restrepo , Kievershen Nargan , Threnesan Naidoo , Daniel L. Clemens , Adrie J.C. Steyn , Vivek V. Thacker , Joanne Turner , Larry S. Schlesinger , 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}
Pub Date : 2024-04-01DOI: 10.1016/j.mucimm.2024.02.008
Bailey J. Didriksen , Emily M. Eshleman , Theresa Alenghat
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.
{"title":"Epithelial regulation of microbiota-immune cell dynamics","authors":"Bailey J. Didriksen , Emily M. Eshleman , 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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.10.005
Iana Gadjalova , Julia M. Heinze , Marie C. Goess , Julian Hofmann , Annalisa Buck , Marie-Christin Weber , Birgit Blissenbach , Maximilian Kampick , Oleg Krut , Katja Steiger , Klaus-Peter Janssen , Philipp-Alexander Neumann , Jürgen Ruland , Selina J. Keppler
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 (Wipf1−/−) 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 Wipf1−/− 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 in vitro, 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.
{"title":"B cell-mediated CD4 T-cell costimulation via CD86 exacerbates pro-inflammatory cytokine production during autoimmune intestinal inflammation","authors":"Iana Gadjalova , Julia M. Heinze , Marie C. Goess , Julian Hofmann , Annalisa Buck , Marie-Christin Weber , Birgit Blissenbach , Maximilian Kampick , Oleg Krut , Katja Steiger , Klaus-Peter Janssen , Philipp-Alexander Neumann , Jürgen Ruland , 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<sup>−/−</sup></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<sup>−/−</sup></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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.11.004
Jacqueline L.E. Tearle , Adelynn Tang , Ajithkumar Vasanthakumar , Kylie R. James
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.
{"title":"Role reversals: non-canonical roles for immune and non-immune cells in the gut","authors":"Jacqueline L.E. Tearle , Adelynn Tang , Ajithkumar Vasanthakumar , 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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.11.005
Dana Costigan , Joe Fenn , Sandi Yen , Nicholas Ilott , Samuel Bullers , Jessica Hale , William Greenhalf , Emily Conibear , Aleksandra Koycheva , Kieran Madon , Ishrat Jahan , Ming Huang , Anjna Badhan , Eleanor Parker , Carolina Rosadas , Kelsey Jones , Myra McClure , Richard Tedder , Graham Taylor , Kenneth J. Baillie , Emily E. Thornton
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.
{"title":"A pro-inflammatory gut mucosal cytokine response is associated with mild COVID-19 disease and superior induction of serum antibodies","authors":"Dana Costigan , Joe Fenn , Sandi Yen , Nicholas Ilott , Samuel Bullers , Jessica Hale , William Greenhalf , Emily Conibear , Aleksandra Koycheva , Kieran Madon , Ishrat Jahan , Ming Huang , Anjna Badhan , Eleanor Parker , Carolina Rosadas , Kelsey Jones , Myra McClure , Richard Tedder , Graham Taylor , Kenneth J. Baillie , 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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.09.007
Hsiang-Han Su , Chih-Mei Cheng , Yung-Ning Yang , Yu-Wei Chang , Chia-Yang Li , Shin-Ting Wu , Chia-Chi Lin , Hsin-En Wu , Jau-Ling Suen
Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or Rag1−/− mice, respectively. The cardinal features of lung inflammation included accumulated infiltration of ILC2s and eosinophils. Transcriptomic analysis revealed a gene expression pattern associated with proliferation-related pathways in acrylamide-treated ILC2s. Western blotting revealed significantly higher expression of Ras and phospho-Erk in acrylamide-treated ILC2s than the control, suggesting Ras-Erk signaling pathway involvement. Ex vivo and in vitro analysis showed that acrylamide treatment mainly increased Ki-67+ ILC2s and the cell number of ILC2s whereas PD98059, a highly selective Erk inhibitor, effectively counteracted the acrylamide effect. Intratracheal administration of acrylamide-treated ILC2s significantly enhanced eosinophil infiltration in Rag1−/− mice. This study suggests that airborne acrylamide may enhance the severity of allergen-induced airway eosinophilic inflammation, partly via altering ILC2 proliferative activity.
{"title":"Acrylamide, an air pollutant, enhances allergen-induced eosinophilic lung inflammation via group 2 innate lymphoid cells","authors":"Hsiang-Han Su , Chih-Mei Cheng , Yung-Ning Yang , Yu-Wei Chang , Chia-Yang Li , Shin-Ting Wu , Chia-Chi Lin , Hsin-En Wu , Jau-Ling Suen","doi":"10.1016/j.mucimm.2023.09.007","DOIUrl":"10.1016/j.mucimm.2023.09.007","url":null,"abstract":"<div><p>Air pollution significantly impacts the aggravation of asthma. Exposure to acrylamide, a volatile organic compound in tobacco smoke, is associated with elevated risks of allergy-related outcomes among active smokers. As group 2 innate lymphoid cells (ILC2s) can act as an environmental sensor and significantly contribute to protease allergen-induced lung inflammation, we aimed to elucidate the causal relationship and how inhaled acrylamide worsens allergic lung inflammation via ILC2s. Intranasal acrylamide exposure at nanomolar levels significantly enhanced allergen-induced or recombinant mouse interleukin-33-induced lung inflammation in C57BL/6 mice or <em>Rag1<sup>−/−</sup></em> mice, respectively. The cardinal features of lung inflammation included accumulated infiltration of ILC2s and eosinophils. Transcriptomic analysis revealed a gene expression pattern associated with proliferation-related pathways in acrylamide-treated ILC2s. Western blotting revealed significantly higher expression of Ras and phospho-Erk in acrylamide-treated ILC2s than the control, suggesting Ras-Erk signaling pathway involvement. <em>Ex vivo</em> and <em>in vitro</em> analysis showed that acrylamide treatment mainly increased Ki-67<sup>+</sup> ILC2s and the cell number of ILC2s whereas PD98059, a highly selective Erk inhibitor, effectively counteracted the acrylamide effect. Intratracheal administration of acrylamide-treated ILC2s significantly enhanced eosinophil infiltration in <em>Rag1<sup>−/−</sup></em> mice. This study suggests that airborne acrylamide may enhance the severity of allergen-induced airway eosinophilic inflammation, partly via altering ILC2 proliferative activity.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 13-24"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000739/pdfft?md5=abf8bfda89aee6fa9b998ebbb125fe89&pid=1-s2.0-S1933021923000739-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41127097","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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.10.001
Stéphane Hua , Krishna Latha , Romain Marlin, Keltouma Benmeziane, Laetitia Bossevot, Sébastien Langlois, Francis Relouzat, Nathalie Dereuddre-Bosquet, Roger Le Grand, Mariangela Cavarelli
SARS-CoV-2 infection has been associated with intestinal mucosal barrier damage, leading to microbial and endotoxin translocation, heightened inflammatory responses, and aggravated disease outcomes. This study aimed to investigate the immunological mechanisms associated with impaired intestinal barrier function. We conducted a comprehensive analysis of gut damage and inflammation markers and phenotypic characterization of myeloid and lymphoid populations in the ileum and colon of SARS-CoV-2-exposed macaques during both the acute and resolved infection phases. Our findings revealed a significant accumulation of terminally differentiated and activated CD4+ and CD8+ T cells, along with memory B cells, within the gastrointestinal tract up to 43 days after exposure to SARS-CoV-2. This robust infection-induced immune response was accompanied by a notable depletion of plasmacytoid dendritic cells, myeloid dendritic cells, and macrophages, particularly affecting the colon during the resolved infection phase. Additionally, we identified a population of CX3CR1Low inflammatory macrophages associated with intestinal damage during active viral replication. Elevated levels of immune activation and gut damage markers, and perturbation of macrophage homeostasis, persisted even after the resolution of the infection, suggesting potential long-term clinical sequelae. These findings enhance our understanding of gastrointestinal immune pathology following SARS-CoV-2 infection and provide valuable information for developing and testing medical countermeasures.
{"title":"Intestinal immunological events of acute and resolved SARS-CoV-2 infection in non-human primates","authors":"Stéphane Hua , Krishna Latha , Romain Marlin, Keltouma Benmeziane, Laetitia Bossevot, Sébastien Langlois, Francis Relouzat, Nathalie Dereuddre-Bosquet, Roger Le Grand, Mariangela Cavarelli","doi":"10.1016/j.mucimm.2023.10.001","DOIUrl":"10.1016/j.mucimm.2023.10.001","url":null,"abstract":"<div><p>SARS-CoV-2 infection has been associated with intestinal mucosal barrier damage, leading to microbial and endotoxin translocation, heightened inflammatory responses, and aggravated disease outcomes. This study aimed to investigate the immunological mechanisms associated with impaired intestinal barrier function. We conducted a comprehensive analysis of gut damage and inflammation markers and phenotypic characterization of myeloid and lymphoid populations in the ileum and colon of SARS-CoV-2-exposed macaques during both the acute and resolved infection phases. Our findings revealed a significant accumulation of terminally differentiated and activated CD4+ and CD8+ T cells, along with memory B cells, within the gastrointestinal tract up to 43 days after exposure to SARS-CoV-2. This robust infection-induced immune response was accompanied by a notable depletion of plasmacytoid dendritic cells, myeloid dendritic cells, and macrophages, particularly affecting the colon during the resolved infection phase. Additionally, we identified a population of CX3CR1<sup>Low</sup> inflammatory macrophages associated with intestinal damage during active viral replication. Elevated levels of immune activation and gut damage markers, and perturbation of macrophage homeostasis, persisted even after the resolution of the infection, suggesting potential long-term clinical sequelae. These findings enhance our understanding of gastrointestinal immune pathology following SARS-CoV-2 infection and provide valuable information for developing and testing medical countermeasures.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 25-40"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193302192300079X/pdfft?md5=966c8ff95accd6eb4b6569cab4335d6c&pid=1-s2.0-S193302192300079X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41205628","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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.10.002
M. Elliott Williams , Felica P. Hardnett , Anandi N. Sheth , Alexander N. Wein , Zheng-Rong Tiger Li , Jessica Radzio-Basu , Chuong Dinh , Lisa B. Haddad , Elizabeth M.B. Collins , Igho Ofotokun , Rustom Antia , Christopher D. Scharer , J. Gerardo Garcia-Lerma , Jacob E. Kohlmeier , Alison Swaims-Kohlmeier
Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell surveillance behaviors by subsets corresponding to migratory memory (TMM) and resident memory T cells. TMM displays tissue-itinerant trafficking characteristics, restricted distribution within the FRT microenvironment, and distinct effector responses to infection. Gene pathway analysis by RNA sequencing identified TMM-specific enrichment of genes involved in hormonal regulation and inflammatory responses. FRT T-cell subset fluctuations were discovered that synchronized to cycle-driven CCR5 signaling. Notably, oral administration of a CCR5 antagonist drug blocked TMM trafficking. Taken together, this study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of immune surveillance at the site of STI pathogen exposure.
{"title":"The menstrual cycle regulates migratory CD4 T-cell surveillance in the female reproductive tract via CCR5 signaling","authors":"M. Elliott Williams , Felica P. Hardnett , Anandi N. Sheth , Alexander N. Wein , Zheng-Rong Tiger Li , Jessica Radzio-Basu , Chuong Dinh , Lisa B. Haddad , Elizabeth M.B. Collins , Igho Ofotokun , Rustom Antia , Christopher D. Scharer , J. Gerardo Garcia-Lerma , Jacob E. Kohlmeier , Alison Swaims-Kohlmeier","doi":"10.1016/j.mucimm.2023.10.002","DOIUrl":"10.1016/j.mucimm.2023.10.002","url":null,"abstract":"<div><p>Despite their importance for immunity against sexually transmitted infections, the composition of female reproductive tract (FRT) memory T-cell populations in response to changes within the local tissue environment under the regulation of the menstrual cycle remains poorly defined. Here, we show that in humans and pig-tailed macaques, the cycle determines distinct clusters of differentiation 4 T-cell surveillance behaviors by subsets corresponding to migratory memory (T<sub>MM</sub>) and resident memory T cells. T<sub>MM</sub> displays tissue-itinerant trafficking characteristics, restricted distribution within the FRT microenvironment, and distinct effector responses to infection. Gene pathway analysis by RNA sequencing identified T<sub>MM</sub>-specific enrichment of genes involved in hormonal regulation and inflammatory responses. FRT T-cell subset fluctuations were discovered that synchronized to cycle-driven CCR5 signaling. Notably, oral administration of a CCR5 antagonist drug blocked T<sub>MM</sub> trafficking. Taken together, this study provides novel insights into the dynamic nature of FRT memory CD4 T cells and identifies the menstrual cycle as a key regulator of immune surveillance at the site of STI pathogen exposure.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 41-53"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1933021923000806/pdfft?md5=d405ae138fb8dd79fd34fde6046024ca&pid=1-s2.0-S1933021923000806-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49691428","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}
Pub Date : 2024-02-01DOI: 10.1016/j.mucimm.2023.10.004
Yifan Niu , Yu Liu , Xiang Ma , Lu Liu , Sihong Li , Rui Li , Tao Wang , Houhui Song , Dong Niu
Endogenous retroelements play vital roles in sustaining immune homeostasis. Activation of endogenous retroelements can trigger cGAS/STING pathway and downstream pro-inflammatory cytokine production. Activated macrophages (M1), which can be induced by pro-inflammatory cytokines, are involved in the development of colitis. Here we aimed to determine whether a retrovirus reverse transcriptase inhibitor azidothymidine (AZT) could influence M1 macrophage polarization and rescue colitis by inhibiting the reverse transcription of murine endogenous retroelements. A dextran sodium sulfate salt (DSS)-induced colitis mouse model (male C57BL/6N) and a lipopolysaccharides-treated RAW264.7 cell line were used to evaluate the protective role of AZT in colitis alleviation. An upregulated expression of endogenous retroelements was first detected in both the colons of the mice with colitis and the lipopolysaccharides-stimulated M1 cells, and treatment with AZT significantly decreased the expression. Meanwhile, a downregulation of cGAS/STING/NF-κB pathway and pro-inflammatory cytokines that induce M1 macrophage polarization was also observed in AZT-treated colitis or M1 groups. Moreover, the symptoms of DSS-induced colitis could be significantly alleviated by AZT. In summary, the endogenous retroelement inhibitor AZT could rescue the DSS-induced colitis possibly via blocking M1 macrophage polarization through cGAS/STING/NF-κB pro-inflammatory pathway. Thus, a pharmacological blockade of endogenous retroelements would be a new strategy for clinical therapy of colitis.
内源性逆源因子在维持免疫平衡方面发挥着重要作用。激活内源性逆转录酶可触发 cGAS/STING 通路和下游促炎细胞因子的产生。激活的巨噬细胞(M1)可由促炎细胞因子诱导,参与结肠炎的发展。在此,我们旨在确定逆转录病毒逆转录酶抑制剂氮卓胸苷(AZT)是否能通过抑制小鼠内源性逆转录病毒的逆转录来影响 M1 巨噬细胞的极化并挽救结肠炎。研究人员使用葡聚糖硫酸钠盐(DSS)诱导的结肠炎小鼠模型(雄性 C57BL/6N)和脂多糖处理的 RAW264.7 细胞系来评估 AZT 在缓解结肠炎方面的保护作用。首先在结肠炎小鼠的结肠和脂多糖刺激的 M1 细胞中都检测到了内源性逆转录酶的上调表达,而用 AZT 治疗可显著降低其表达。同时,在 AZT 治疗的结肠炎组或 M1 组中,还观察到 cGAS/STING/NF-κB 通路和诱导 M1 巨噬细胞极化的促炎细胞因子的下调。此外,AZT 还能显著缓解 DSS 诱导的结肠炎症状。综上所述,内源性逆转录酶抑制剂 AZT 可通过 cGAS/STING/NF-κB 促炎途径阻断 M1 巨噬细胞极化,从而缓解 DSS 诱导的结肠炎。因此,药物阻断内源性逆转录酶将成为临床治疗结肠炎的新策略。
{"title":"Disrupting endogenous retroelements with a reverse transcriptase inhibitor alleviates DSS-induced colitis in mice","authors":"Yifan Niu , Yu Liu , Xiang Ma , Lu Liu , Sihong Li , Rui Li , Tao Wang , Houhui Song , Dong Niu","doi":"10.1016/j.mucimm.2023.10.004","DOIUrl":"10.1016/j.mucimm.2023.10.004","url":null,"abstract":"<div><p>Endogenous retroelements play vital roles in sustaining immune homeostasis. Activation of endogenous retroelements can trigger cGAS/STING pathway and downstream pro-inflammatory cytokine production. Activated macrophages (M1), which can be induced by pro-inflammatory cytokines, are involved in the development of colitis. Here we aimed to determine whether a retrovirus reverse transcriptase inhibitor azidothymidine (AZT) could influence M1 macrophage polarization and rescue colitis by inhibiting the reverse transcription of murine endogenous retroelements. A dextran sodium sulfate salt (DSS)-induced colitis mouse model (male C57BL/6N) and a lipopolysaccharides-treated RAW264.7 cell line were used to evaluate the protective role of AZT in colitis alleviation. An upregulated expression of endogenous retroelements was first detected in both the colons of the mice with colitis and the lipopolysaccharides-stimulated M1 cells, and treatment with AZT significantly decreased the expression. Meanwhile, a downregulation of cGAS/STING/NF-κB pathway and pro-inflammatory cytokines that induce M1 macrophage polarization was also observed in AZT-treated colitis or M1 groups. Moreover, the symptoms of DSS-induced colitis could be significantly alleviated by AZT. In summary, the endogenous retroelement inhibitor AZT could rescue the DSS-induced colitis possibly via blocking M1 macrophage polarization through cGAS/STING/NF-κB pro-inflammatory pathway. Thus, a pharmacological blockade of endogenous retroelements would be a new strategy for clinical therapy of colitis.</p></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"17 1","pages":"Pages 54-66"},"PeriodicalIF":8.0,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S193302192300082X/pdfft?md5=8613df83c1da4bc7f2b6d608943544f9&pid=1-s2.0-S193302192300082X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136127443","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}