Mucosal Immunology最新文献

{"title":"Antibiotic-Induced dysbiosis of the ocular microbiome affects corneal circadian rhythmic activity in mice.","authors":"Xinwei Jiao, Yan Li, Yu Hu, Ruyu Yan, Ting Fu, Jun Liu, Zhijie Li","doi":"10.1016/j.mucimm.2025.01.010","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.01.010","url":null,"abstract":"<p><p>The ocular surface microbiota plays a critical role in maintaining corneal homeostasis, but its disruption and subsequent effects on corneal functions remain poorly understood. This study investigates how antibiotic-induced microbial depletion affects the corneal circadian transcriptome in C57BL/6J mice. Dysbiosis was induced using a topical antibiotic cocktail, and RNA sequencing was employed to analyze gene expression across eight time points over 24 h. Antibiotic treatment disrupted corneal circadian rhythms, eliminating rhythmicity in 1,812 genes and introducing rhythmicity in 1,928 previously arrhythmic genes. Furthermore, epithelial adhesion was impaired, inflammation was elevated, and neural sensitivity was reduced. More than 50 % of ocular microbial genera exhibited daily oscillations, with six genera showing significant correlations with corneal rhythmic transcripts. Additionally, the administration of TLR agonists restored circadian gene expression patterns, with partial recovery of corneal barrier function and immune homeostasis, further highlighting the potential of microbiota-targeted therapies in treating ocular surface disorders. These findings underscore the critical role of the ocular microbiota in regulating corneal health and suggest that restoring microbial balance via TLR activation may offer new therapeutic avenues for eye diseases.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374452","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":"Mitochondrial damage-associated molecular patterns: New perspectives for mitochondria and inflammatory bowel diseases.","authors":"Zhijie Wang, Zixuan He, Xin Chang, Lu Xie, Yihang Song, Haicong Wu, Hao Zhang, Shuling Wang, Xiaofeng Zhang, Yu Bai","doi":"10.1016/j.mucimm.2025.01.013","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.01.013","url":null,"abstract":"<p><p>Mitochondria are key regulators of inflammatory responses and mitochondrial dysfunction is closely linked to various inflammatory diseases. Increasing genetic and experimental evidence suggests that mitochondria play a critical role in inflammatory bowel disease (IBD). In the complex environment of the intestinal tract, intestinal epithelial cells (IECs) and their mitochondria possess unique phenotypic features, shaping each other and regulating intestinal homeostasis and inflammation through diverse mechanisms. Here, we focus on intestinal inflammation in IBD induced by mitochondrial damage-associated molecular patterns (mtDAMPs), which comprise mitochondrial components and metabolic products. The pathogenic mechanisms of mtDAMP signaling pathways mediated by two major mtDAMPs, mitochondrial DNA (mtDNA) and mitochondrial reactive oxygen species (mtROS), are discussed.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374453","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, Alanna M Kelly, Matthew R Hepworth","doi":"10.1016/j.mucimm.2025.01.012","DOIUrl":"10.1016/j.mucimm.2025.01.012","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","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":"Tear duct M cells exacerbate allergic conjunctivitis by facilitating germinal-center reactions.","authors":"Yuki Oya, Shunsuke Kimura, Maho Uemura, Yumiko Fujimura, Koji Hase","doi":"10.1016/j.mucimm.2025.01.009","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.01.009","url":null,"abstract":"<p><p>The ocular mucosal surface regularly encounters external materials in the air and tear fluids. Microfold (M) cells, specialized epithelial cells for antigen uptake, are present in tear duct-associated lymphoid tissue (TALT) within the nasolacrimal sac; however, their immunological significance is unclear. We generated Krt5-Cre Tnfrsf11a^flox/flox mice, which lack functional M cells in the TALT, as evidenced by the absence of M-cell markers and reduced nanoparticle uptake. M cell deficiency resulted in fewer T follicular helper (Tfh) and germinal center (GC) B cells in the TALT under steady-state conditions. Upon induction of allergic conjunctivitis, control mice exhibited itching and increased Tfh and immunoglobulin E (IgE⁺) GC B cells in the TALT. However, M cell-deficient mice showed ameliorated allergic symptoms with fewer Tfh and IgE⁺ GC B cells. These findings suggest that M cells in TALT contribute to ocular surface immunosurveillance, whereas, upon allergen exposure, they play a critical role in the development of allergic conjunctivitis.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143122946","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":"Microbial remodeling of gut tryptophan metabolism and indole-3-lactate production regulate epithelial barrier repair and viral suppression in human and simian immunodeficiency virus infections.","authors":"Clarissa Santos Rocha, Katie L Alexander, Carolina Herrera, Mariana G Weber, Irina Grishina, Lauren A Hirao, Dylan J Kramer, Juan Arredondo, Abigail Mende, Katti R Crakes, Anne N Fenton, Maria L Marco, David A Mills, John C Kappes, Lesley E Smythies, Paul Ziprin, Sumathi Sankaran-Walters, Phillip D Smith, Satya Dandekar","doi":"10.1016/j.mucimm.2025.01.011","DOIUrl":"10.1016/j.mucimm.2025.01.011","url":null,"abstract":"<p><p>Gut inflammatory diseases cause microbial dysbiosis. Human immunodeficiency virus-1 (HIV) infection disrupts intestinal integrity, subverts repair/renewal pathways, impairs mucosal immunity and propels microbial dysbiosis. However, microbial metabolic mechanisms driving repair mechanisms in virally inflamed gut are not well understood. We investigated the capability and mechanisms of gut microbes to restore epithelial barriers and mucosal immunity in virally inflamed gut by using a multipronged approach: an in vivo simian immunodeficiency virus (SIV)-infected nonhuman primate model of HIV/AIDS, ex vivo HIV-exposed human colorectal explants and primary human intestinal epithelial cells. SIV infection reprogrammed tryptophan (TRP) metabolism, increasing kynurenine catabolite levels that are associated with mucosal barrier disruption and immune suppression. Administration of Lactiplantibacillus plantarum or Bifidobacterium longum subsp. infantis into the SIV-inflamed gut lumen in vivo resulted in rapid reprogramming of microbial TRP metabolism towards indole-3-lactic acid (ILA) production. This shift accelerated epithelial repair and enhanced anti-viral defenses through induction of IL-22 signaling in mucosal T cells and aryl hydrocarbon receptor activation. Additionally, ILA treatment of human colorectal tissue explants ex vivo inhibited HIV replication by reducing mucosal inflammatory cytokine production and cell activation. Our findings underscore the therapeutic potential of microbial metabolic reprogramming of TRP-to-ILA and mechanisms in mitigating viral pathogenic effects and bolstering mucosal defenses for HIV eradication.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080673","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":"Damage sensing through TLR9 regulates inflammatory and antiviral responses during influenza infection.","authors":"Jooyoung Kim, Yifan Yuan, Karen Agaronyan, Amy Zhao, Victoria D Wang, David Gau, Nicholas Toosi, Gayatri Gupta, Heran Essayas, Ayelet Kaminski, John McGovern, Sheeline Yu, Samuel Woo, Chris J Lee, Shifa Gandhi, Tina Saber, Tayebeh Saleh, Buqu Hu, Ying Sun, Genta Ishikawa, William Bain, John Evankovich, Lujia Chen, Hong Duck Yun, Erica L Herzog, Charles S Dela Cruz, Changwan Ryu, Lokesh Sharma","doi":"10.1016/j.mucimm.2025.01.008","DOIUrl":"10.1016/j.mucimm.2025.01.008","url":null,"abstract":"<p><p>Host response aimed at eliminating the infecting pathogen, as well as the pathogen itself, can cause tissue injury. Tissue injury leads to the release of a myriad of cellular components including mitochondrial DNA, which the host senses through pattern recognition receptors. How the sensing of tissue injury by the host shapes the anti-pathogen response remains poorly understood. In this study, we utilized mice that are deficient in toll-like receptor-9 (TLR9), which binds to unmethylated CpG DNA sequences such as those present in bacterial and mitochondrial DNA. To avoid direct pathogen sensing by TLR9, we utilized the influenza virus, which lacks ligands for TLR9, to determine how damage sensing by TLR9 contributes to anti-influenza immunity. Our data show that TLR9-mediated sensing of tissue damage promotes an inflammatory response during early infection, driven by the epithelial and myeloid cells. Along with the diminished inflammatory response, the absence of TLR9 led to impaired viral clearance manifested as a higher and prolonged influenza components in myeloid cells including monocytes and macrophages rendering them highly inflammatory. The persistent inflammation driven by infected myeloid cells led to persistent lung injury and impaired recovery in influenza-infected TLR9-/- mice. Further, we show elevated TLR9 activation in the plasma samples of patients with influenza and its association with the disease severity in hospitalized patients, demonstrating its clinical relevance. Overall, we demonstrate an essential role of damage sensing through TLR9 in promoting anti-influenza immunity and inflammatory response AUTHOR SUMMARY: Tissue damage is an inevitable outcome of clinically relevant lung infections, but the host mechanisms for detecting such damage during infection are not well understood. We investigated the role of Toll-like receptor 9 (TLR9) in sensing tissue damage caused by influenza. Since influenza lacks TLR9 ligands, we hypothesized that TLR9 signaling is driven by tissue damage molecules like mitochondrial DNA (mtDNA). Our data indicate that TLR9 reduces early inflammatory lung injury but impairs viral clearance, resulting in extensive immune cell infection, persistent inflammation, and delayed recovery. Myeloid-specific TLR9 deletion ameliorated late-stage inflammatory responses. In humans, influenza-infected individuals exhibited elevated TLR9 activity and mtDNA levels in plasma compared to healthy controls, with higher TLR9 activation potential correlating with severe disease requiring ICU admission. These findings suggest that TLR9-mediated damage sensing triggers both inflammatory tissue injury and viral clearance. These data indicate that TLR9 activity can serve as a crucial biomarker and therapeutic target to limit influenza induced tissue injury.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143066829","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, Jessica Lakshmi Prieto-Chávez, Claudia Angélica García-Alonso, Anna-Maria Lampousi, Mario R Alcorta-García, Víctor J Lara-Diaz, Claudia N López-Villaseñor, Marion E G Brunck","doi":"10.1016/j.mucimm.2025.01.007","DOIUrl":"10.1016/j.mucimm.2025.01.007","url":null,"abstract":"<p><p>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 > 30 kg/m² (21 and 16 mothers, respectively) were collected 24-48 h postpartum. 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 > 30 kg/m² contained significantly more IgG-secreting colostrum-resident B cells, more total IgG, and less total IgA. Mothers with BMI > 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.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-25","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":"Lifelong partners: Gut microbiota-immune cell interactions from infancy to old age.","authors":"Julia A Brown, Hilal Bashir, Melody Y Zeng","doi":"10.1016/j.mucimm.2025.01.006","DOIUrl":"10.1016/j.mucimm.2025.01.006","url":null,"abstract":"<p><p>Our immune system and gut microbiota are intricately coupled from birth, both going through maturation during early life and senescence during aging almost in a synchronized fashion. The symbiotic relationship between the human host and microbiota is critically dependent on a healthy immune system to keep our microbiota in check, while the microbiota provides essential functions to promote the development and fitness of our immune system. The partnership between our immune system and microbiota is particularly important during early life, when microbial ligands and metabolites shape the development of the immune cells and immune tolerance; during aging, having sufficient beneficial gut bacteria is critical for the maintenance of intact mucosal barriers, immune metabolic fitness, and strong immunity against pathogens. The immune system during childhood is programmed, with the support of the microbiota, to develop robust immune tolerance, and limit autoimmunity and metabolic dysregulation, which are prevalent during aging. This review comprehensively explores the mechanistic underpinnings of gut microbiota-immune cell interactions during infancy and old age, with the goal to gain a better understanding of potential strategies to leverage the gut microbiota to combat age-related immune decline.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143040338","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":"Corrigendum to \"Stress systems exacerbate the inflammatory response after corneal abrasion in sleep-deprived mice via the IL-17 signaling pathway\" [Mucosal Immunol. 17(3) (2024) 323-345].","authors":"Yunxia Xue, Pengyang Xu, Yu Hu, Sijing Liu, Ruyu Yan, Shutong Liu, Yan Li, Jun Liu, Ting Fu, Zhijie Li","doi":"10.1016/j.mucimm.2025.01.001","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.01.001","url":null,"abstract":"","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023979","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":"Breast milk delivery of an engineered dimeric IgA protects neonates against rotavirus.","authors":"Stephanie N Langel, Claire E Otero, Justin T Steppe, Caitlin A Williams, Tatiana Travieso, Jerry Chang, Helen Webster, Lauren E Williamson, James E Crowe, Harry B Greenberg, Huali Wu, Christoph P Hornik, Katayoun Mansouri, Robert J Edwards, Victoria Stalls, Priyamvada Acharya, Maria Blasi, Sallie R Permar","doi":"10.1016/j.mucimm.2025.01.002","DOIUrl":"10.1016/j.mucimm.2025.01.002","url":null,"abstract":"<p><p>Dimeric IgA (dIgA) is the dominant antibody in many mucosal tissues. It is actively transported onto mucosal surfaces as secretory IgA (sIgA) which plays an integral role in protection against enteric pathogens, particularly in young children. Therapeutic strategies that deliver engineered, potently neutralizing antibodies directly into the infant intestine through breast milk could provide enhanced antimicrobial protection for neonates. Here, we developed a murine model of maternal protective transfer against human rotavirus (RV) using systemic administration of a dimeric IgA monoclonal antibody (mAb). First, we showed that systemically administered dIgA passively transferred into breast milk and the stomach of suckling pups in a dose-dependent manner. Next, we optimized the recombinant production of a potently RV-neutralizing, VP4-specific dIgA (mAb41) antibody. We then demonstrated that systemic administration of dIgA and IgG mAb41 in lactating dams conferred protection from RV-induced diarrhea in suckling pups, with dIgA resulting in lower diarrhea incidence from IgG. Systemic delivery of engineered antimicrobial dIgA mAbs should be considered as an effective strategy for sIgA delivery to the infant gastrointestinal tract via breast milk to increase protection against enteric pathogens.</p>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.9,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023749","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}