Mucosal Immunology最新文献

{"title":"Living on the edge: Mucus-associated microbes in the colon.","authors":"Mihovil Joja, Erica T Grant, Mahesh S Desai","doi":"10.1016/j.mucimm.2025.04.003","DOIUrl":"10.1016/j.mucimm.2025.04.003","url":null,"abstract":"<p><p>The colonic mucus layer acts as a physicochemical barrier to pathogen invasion and as a habitat for mucus-associated microbes. This mucosal microbiome plays a crucial role in moderating mucus production, maintaining barrier integrity, and shaping the host immune response. However, unchecked mucin foraging may render the host vulnerable to disease. To better understand these dynamics in the mucus layer, it is essential to advance fundamental knowledge on how commensals bind to and utilize mucin as well as their interactions with both the host and their microbial neighbors. We present an overview of approaches for surveying mucus-associated bacteria and assessing their mucin-utilizing capacity, alongside a discussion of the limitations of existing methods. Additionally, we highlight how diet and host secretory immunoglobulin A interact with the mucosal bacterial community in the colon. Insights into this subset of the microbial community can guide therapeutic strategies to optimally support and modulate mucosal barrier integrity.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144028688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A multi-omics microbiome signature is associated with the benefits of gastric bypass surgery and is differentiated from diet induced weight loss through 2 years of follow-up.","authors":"Vancheswaran Gopalakrishnan, Chanchal Kumar, Ida Robertsen, Christopher Morehouse, Ben Sparklin, Shameer Khader, Ian Henry, Line Kristin Johnson, Jens K Hertel, Hege Christensen, Rune Sandbu, Peter J Greasley, Bret R Sellman, Anders Åsberg, Shalini Andersson, Rasmus Jansson Löfmark, Jøran Hjelmesæth, Cecilia Karlsson, Taylor S Cohen","doi":"10.1016/j.mucimm.2025.04.002","DOIUrl":"10.1016/j.mucimm.2025.04.002","url":null,"abstract":"<p><p>Roux-en-Y gastric bypass (GBP) surgery is an effective treatment for reducing body weight and correcting metabolic dysfunction in individuals with severe obesity. Herein, we characterize the differences between very low energy diet (VLED) and GBP induced weight loss by multi-omic analyses of microbiome and host features in a non-randomized, controlled, single-center study. Eighty-eight participants with severe obesity were recruited into two arms - GBP versus VLED with matching weight loss for 6 weeks and 2-years of follow-up. A dramatic shift in the distribution of gut microbial taxa and their functional capacity was seen in the GBP group at Week 2 after surgery and was sustained through 2 years. Multi-omic analyses were performed after 6 weeks of matching weight loss between the GBP and VLED groups, which pointed to microbiome derived metabolites such as indoxyl sulphate as characterizing the GBP group. We also identified an inverse association between Streptococcus parasanguinis (an oral commensal) and plasma levels of tryptophan and tyrosine. These data have important implications, as they reveal a significant robust restructuring of the microbiome away from a baseline dysbiotic state in the GBP group. Furthermore, multi-omics modelling points to potentially novel mechanistic insights at the intersection of the microbiome and host.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993830","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innate immunity of the lungs in homeostasis and disease.","authors":"Peter A A Norris, Paul Kubes","doi":"10.1016/j.mucimm.2025.04.001","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.04.001","url":null,"abstract":"<p><p>Humans breathe thousands of litres of non-sterile air each day containing bacteria, viruses, and fungi, as well as pollutants, allergens, and other particles. The continual exposure to foreign particles is juxtaposed with the vast surface area of the blood-air-barrier which becomes extremely thin to allow for efficient gas exchange. To prevent infection and injury, the healthy lung relies on a robust innate immune system to protect itself. Critically, this innate immune system must clear insults while maintaining immune tolerance and minimizing inflammation to avoid disrupting the lung's vital gas exchange function. In this review, we discuss how the innate immune system protects the lung from its environment.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sialidase fusion protein protects against influenza infection in a cigarette smoke-induced model of COPD","authors":"Cheng-Yen Chang ,&nbsp;Dominique Armstrong ,&nbsp;John M. Knight ,&nbsp;Trevor V. Gale ,&nbsp;Stephen Hawley ,&nbsp;Max Wang ,&nbsp;Nancy Chang ,&nbsp;David B. Corry ,&nbsp;Farrah Kheradmand","doi":"10.1016/j.mucimm.2025.01.004","DOIUrl":"10.1016/j.mucimm.2025.01.004","url":null,"abstract":"<div><div>First- and secondhand smokers are at an increased risk for influenza virus (IFV)-related respiratory failure and death. Despite approved influenza antiviral treatments, there is an unmet need for treatments that can improve outcomes in populations at risk for respiratory failure, including tobacco users with Chronic Obstructive Pulmonary Disease (COPD). Here we show that the sialidase fusion protein, DAS181, reduced viral burden, mitigated inflammation, and attenuated lung function loss, consistent with broad-spectrum anti-influenza responses in a mouse model of COPD and IFV-A infection. Treatment with DAS181 reprogramed the sialic acid-binding immunoglobulin-like lectins (Siglecs) in alveolar macrophages, increased expression of phagocytic marker CD169, and downregulated inhibitory Siglec-F and Siglec-H molecules. Upon reinfection, mice treated with DAS181 showed activated and protective memory response in the lungs. Collectively, we show that this sialidase fusion protein promotes a beneficial immunomodulatory reaction in the lungs, supporting a new IFV-A therapeutic option for at-risk smokers.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 467-480"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"There’s no place like home: How local tissue microenvironments shape the function of innate lymphoid cells","authors":"Luke B. Roberts ,&nbsp;Alanna M. Kelly ,&nbsp;Matthew R. Hepworth","doi":"10.1016/j.mucimm.2025.01.012","DOIUrl":"10.1016/j.mucimm.2025.01.012","url":null,"abstract":"<div><div>Innate lymphoid cells (ILC) have emerged as critical immune effectors with key roles in orchestrating the wider immune response. While ILC are relatively rare cells they are found enriched within discrete microenvironments, predominantly within barrier tissues. An emerging body of evidence implicates complex and multi-layered interactions between cell types, tissue structure and the external environment as key determinants of ILC function within these niches. In this review we will discuss the specific components that constitute ILC-associated microenvironments and consider how they act to determine health and disease. The development of holistic, integrated models of ILC function within complex tissue environments will inform new understanding of the contextual cues and mechanisms that determine the protective versus disease-causing roles of this immune cell family.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 279-289"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decidualization-associated recruitment of cytotoxic memory CD8+T cells to the maternal-fetal interface for immune defense","authors":"Xixi Huang ,&nbsp;Tingxuan Yin ,&nbsp;Min Yu ,&nbsp;Guohua Zhu ,&nbsp;Xianyang Hu ,&nbsp;Hailin Yu ,&nbsp;Weijie Zhao ,&nbsp;Jiajia Chen ,&nbsp;Jiangyuan Du ,&nbsp;Qingyu Wu ,&nbsp;Wei Zhang ,&nbsp;Lu Liu ,&nbsp;Meirong Du","doi":"10.1016/j.mucimm.2024.12.007","DOIUrl":"10.1016/j.mucimm.2024.12.007","url":null,"abstract":"<div><div>Decidual CD8⁺T (dCD8⁺T) cells are pivotal in the maintenance of the delicate balance between immune tolerance towards the fetus and immune resistance against pathogens. The endometrium and decidua represent the uterine environments before and during pregnancy, respectively, yet the composition and phenotypic alterations of uterine CD8⁺T cells in these tissues remain unclear. Using flow cytometry and analysis of transcriptome profiles, we demonstrated that human dCD8⁺T and endometrial CD8⁺T (eCD8⁺T) cells exhibited similar T cell differentiation statuses and phenotypes of tissue infiltrating or residency, compared to peripheral CD8⁺T (pCD8⁺T) cells. However, dCD8⁺T cells showed decreased expression of coinhibitory marker (PD-1), chemotaxis marker (CXCR3), and tissue-resident markers (CD69 and CD103), along with increased expression of granzyme B and granulysin, compared to eCD8⁺T cells. In vitro cytotoxicity assays further demonstrated that dCD8⁺T cells had greater effector functions than eCD8⁺T cells. Additionally, both in vitro and in vivo chemotaxis assays confirmed the recruitment of non-resident effector memory T cell subsets to the pregnant decidua, contributing to the dCD8⁺T cell-mediated anti-infection mechanism at the maternal-fetal interface. This work demonstrates dCD8⁺T cells replenished from the circulation retain their cytotoxic capacity, which may serve as an enhanced defense mechanism against infection during pregnancy.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 366-379"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142829344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"T follicular helper cell expansion and hyperimmunoglobulinemia with spontaneous IgE production to dietary antigens in IgA-deficient mice","authors":"Yasmeen S. El Ansari ,&nbsp;Cynthia Kanagaratham ,&nbsp;Kameryn N. Furiness ,&nbsp;Kailey E. Brodeur ,&nbsp;Pui Y. Lee ,&nbsp;Harald Renz ,&nbsp;Hans C. Oettgen","doi":"10.1016/j.mucimm.2025.01.005","DOIUrl":"10.1016/j.mucimm.2025.01.005","url":null,"abstract":"<div><div>Immunoglobulin A (IgA), the most abundantly produced antibody at mucosal surfaces, is thought to play key roles in immune responses to respiratory and enteric pathogens and in the regulation of commensal colonization. Low IgA levels have been associated with recurrent infections and immune dysregulation, including inflammatory bowel disease and autoimmunity. Levels of IgA in maternal breast milk and infant stool are both inversely associated with the emergence of immune responses to food antigens in infants and, in naturally resolving food sensitivity and immunotherapy protocols, the induction of IgA antibodies to dietary antigens has been associated with the acquisition of food tolerance. Here, we uncover new roles for IgA in intestinal immune homeostasis utilizing IgA Knockout (KO) mice generated by CRISPR/Cas9. IgA-deficient mice exhibit hyperimmunoglobulinemia, with increased levels of IgE and MCPT-1. The hyperimmunoglobulinemia is associated with dysregulated Tfh/Tfr responses in the Peyer’s Patches (PPs) and spontaneous immunoglobulin production to chow diet. These findings shed light on important interactions between IgA, the mucosal immune system, and the regulation of Tfh responses, emphasizing the importance of IgA in maintaining immune homeostasis at mucosal surfaces.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 481-490"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NOD1 signaling regulates early tissue inflammation during helminth infection","authors":"Camila de Almeida Lopes ,&nbsp;Thais Leal-Silva ,&nbsp;Flaviane Vieira-Santos ,&nbsp;Jorge Lucas Nascimento Souza ,&nbsp;Chiara Cassia Amorim Oliveira ,&nbsp;Fabricio Marcus Silva Oliveira ,&nbsp;Lucas Kraemer ,&nbsp;Luisa Magalhaes ,&nbsp;Pablo Bara-Garcia ,&nbsp;Byunghyun Kang ,&nbsp;Dario Zamboni ,&nbsp;Remo Castro Russo ,&nbsp;Ricardo Toshio Fujiwara ,&nbsp;Thomas B. Nutman ,&nbsp;Pedro Gazzinelli-Guimaraes ,&nbsp;Lilian Lacerda Bueno","doi":"10.1016/j.mucimm.2024.12.004","DOIUrl":"10.1016/j.mucimm.2024.12.004","url":null,"abstract":"<div><div>The role of innate receptors in initiating the early inflammatory response to helminth larval stages in affected tissues during their life cycle within the host remains poorly understood. Given its pivotal role in detecting microbial elements and eliciting immune responses, exploring the NOD1 receptor could offer crucial insights into immune responses to parasitic infections. By using the larval ascariasis model, the acute model for early <em>Ascaris</em> sp. infection in humans, we report that NOD1 signaling markedly regulates pulmonary tissue inflammation during <em>Ascaris</em> larval migration. Here we show that <em>Ascaris</em>-infected NOD1-deficient mice exhibited a pronounced decrease in macrophage and eosinophil recruitment to the lungs. This diminished cellular recruitment to the lung correlated with impaired production of a mixed cytokine profile including IFN-γ, IL-1β, IL-5, IL-10, IL-17 and IL-33. The attenuated inflammatory response observed in the absence of NOD1 signaling during infection was associated with a notable amelioration in lung dysfunction compared to WT-infected mice. Systemically, NOD1 signaling was also associated with <em>Ascaris</em>-specific IgG2b antibody responses. In summary, our findings highlight a pathogenic role for NOD1 signaling in <em>Ascaris</em>-induced tissue inflammation, underlying hematopoietic cell recruitment and regulating downstream inflammatory cascades associated with the host’s innate immune responses in the tissue triggered by helminth larval migration.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 339-352"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal obesity associates with altered humoral immunity in blood and colostrum","authors":"Erick S. Sánchez-Salguero ,&nbsp;Jessica Lakshmi Prieto-Chávez ,&nbsp;Claudia Angélica García-Alonso ,&nbsp;Anna-Maria Lampousi ,&nbsp;Mario R. Alcorta-García ,&nbsp;Víctor J. Lara-Diaz ,&nbsp;Claudia N. López-Villaseñor ,&nbsp;Marion E.G. Brunck","doi":"10.1016/j.mucimm.2025.01.007","DOIUrl":"10.1016/j.mucimm.2025.01.007","url":null,"abstract":"<div><div>Maternal obesity is a condition with increasing prevalence worldwide, that correlates with negative infant outcomes. Here we performed an observational cross-sectional study, where peripheral blood and colostrum samples from 37 mothers with BMI between 18.5–25 or &gt; 30 kg/m² (21 and 16 mothers, respectively) were collected 24–48 h <em>postpartum</em>. B lymphocyte subpopulations were investigated using flow cytometry. IgG, IgA, and IgM concentrations, and antibody production from colostrum-resident B cells were quantified. Overall, naïve B lymphocytes were the most abundant subtype in peripheral blood, while CD27^-IgD^- double-negative B cells were the most frequent in colostrum. The colostrum from mothers with BMI &gt; 30 kg/m² contained significantly more IgG-secreting colostrum-resident B cells, more total IgG, and less total IgA. Mothers with BMI &gt; 30 kg/m² who had been vaccinated with the Pfizer BioNTech bivalent vaccine during the third trimester of pregnancy (n = 8) did not show higher IgA or IgG antibody responses against SARS-CoV-2 RBD in either tissue types compared to unvaccinated mothers, contrasting with mother of BMI between 18.5–25 kg/m² (n = 7). This is the first characterization of B lymphocyte subpopulations and antibodies in the colostrum of mothers with obesity. This work uncovers maternal obesity as a possible modifier of humoral immune components in colostrum.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 491-499"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143053128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Early life microbiota colonization programs nociceptor sensitivity by regulating NGF production in mast cells","authors":"Nasser S. Abdullah ,&nbsp;Amyaouch Bradaia ,&nbsp;Manon Defaye ,&nbsp;Christina Ohland ,&nbsp;Kristofer Svendsen ,&nbsp;Anabel Dickemann ,&nbsp;Melissa Delanne-Cumenal ,&nbsp;Ahmed Hassan ,&nbsp;Mircea Iftinca ,&nbsp;Kathy D. McCoy ,&nbsp;Christophe Altier","doi":"10.1016/j.mucimm.2024.12.002","DOIUrl":"10.1016/j.mucimm.2024.12.002","url":null,"abstract":"<div><div>Recent evidence suggests that the gut microbiota can influence pain sensitivity, highlighting the potential for microbiota-targeted pain interventions. During early life, both the microbiota and nociceptors are fine-tuned and respond to environmental factors, however, little is known about how they interact with each other. Using germ-free and gnotobiotic models, we demonstrate that microbiota colonization controls nociceptor sensitivity, partly by modulating mast cell production of nerve growth factor (NGF). We report that germ-free mice respond less to thermal and capsaicin-induced stimulation, which correlates with reduced trafficking of TRPV1 to the cell membrane of nociceptors. In germ-free mice, mast cells express lower levels of NGF. Hyposensitivity to thermal and capsaicin-induced stimulation, reduced TRPV1 trafficking, and decreased NGF expression are reversed when mice are colonized at birth, but not when colonization occurs after weaning. Inhibition of mast cell degranulation and NGF signaling during the first weeks of life in colonized mice leads to a hyposensitive phenotype in adulthood, demonstrating a role for mast cells and NGF signaling in linking early life colonization with nociceptor sensitivity. These findings implicate the early life microbiota in shaping mast cell NGF production and nociceptor sensitivity later in life.</div></div><div><h3>Significance Statement</h3><div>Nociceptors are specialized sensory neurons that detect and transduce painful stimuli. During the early postnatal period, nociceptors are influenced by sensory experiences and the environment. Our findings demonstrate that gut microbiota colonization is essential in setting the threshold of nociceptor responses to painful stimuli. We show that early-life bacterial colonization controls the production of nerve growth factor by mast cells, affecting our sensitivity to pain later in life. Our study highlights the potential for developing new pain treatments that target the gut microbiome.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 2","pages":"Pages 326-338"},"PeriodicalIF":7.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142813823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}