Mucosal Immunology最新文献_第4页

Microbiota-derived tryptophan metabolites shape Th2 lymphocyte responses via the aryl hydrocarbon receptor and metabolic reprogramming. 微生物源色氨酸代谢物通过芳烃受体和代谢重编程形成Th2淋巴细胞反应。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-09-18 DOI: 10.1016/j.mucimm.2026.100405

Lu Yao, Tanya Guevara Avella, Abhijeet J Kulkarni, Marlinde Waardenburg, Maria Isabel Delgado-Dolset, Tomasz Wypych, Avril Walters, Kristoff Nieves, Hannah Devotta, Songhui Kim, Emer Shannon, Nonhlanhla Lunjani, Jens Walter, Milena Sokolowska, Liam O'Mahony

{"title":"Microbiota-derived tryptophan metabolites shape Th2 lymphocyte responses via the aryl hydrocarbon receptor and metabolic reprogramming.","authors":"Lu Yao, Tanya Guevara Avella, Abhijeet J Kulkarni, Marlinde Waardenburg, Maria Isabel Delgado-Dolset, Tomasz Wypych, Avril Walters, Kristoff Nieves, Hannah Devotta, Songhui Kim, Emer Shannon, Nonhlanhla Lunjani, Jens Walter, Milena Sokolowska, Liam O'Mahony","doi":"10.1016/j.mucimm.2026.100405","DOIUrl":"10.1016/j.mucimm.2026.100405","url":null,"abstract":"Allergic diseases are linked with changes in gut microbiota composition and metabolism, but the direct mechanisms linking microbial metabolism to T helper 2 (Th2) lymphocyte differentiation are still poorly understood. Colonization of gnotobiotic animals with Bifidobacterium longum and Clostridium sporogenes resulted in high levels of tryptophan-derived indole-3-lactic acid (ILA), indole-3-acrylic acid (IA), and indole-3-propionic acid (IPA), which correlated with suppressed Th2 responses. Indoxyl-3-sulfate (I3S) and IA reduced interleukin (IL)-4, IL-5 and IL-13 secretion from human Th2 polarized lymphocytes in an aryl-hydrocarbon receptor (AHR)-dependent manner. IA and IPA induced broader metabolic rewiring by reducing Th2 cell mitochondrial oxidative phosphorylation and reactive oxygen species damage. Microbial tryptophan metabolism may modulate human Th2 cell polarization, differentiation and function thereby linking allergy development to microbial processes. In addition, we have identified novel links between mitochondrial metabolic programs and Th2 lymphocyte polarization that are impacted by the microbial Stickland pathway derived metabolites IA and IPA.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100405"},"PeriodicalIF":5.5,"publicationDate":"2026-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149002225","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}

引用次数: 0

Mucosal-associated invariant T cells respond to colonic microbiome alterations during acute HIV infection. 急性HIV感染期间，粘膜相关的不变性T细胞对结肠微生物组改变作出反应。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-09-10 DOI: 10.1016/j.mucimm.2026.100403

Sinmanus Vimonpatranon, Sydney K Mika, Alina P S Pang, Kawthar Machmach, Noemia S Lima, Sucheta Godbole, Chayada Sajjaweerawan, Elizabeth R Longtine, Amy R Henry, Farida Laboune, Ellie Metz, Nisakorn Ratnaratorn, Yuwadee Phuang-Ngern, Carlo Sacdalan, Julie A Ake, Barbara L Shacklett, Johan K Sandberg, Rungsun Rerknimitr, Nittaya Phanuphak, Sandhya Vasan, Daniel C Douek, Michael J Corley, Alexandra Schuetz, Dominic Paquin-Proulx

{"title":"Mucosal-associated invariant T cells respond to colonic microbiome alterations during acute HIV infection.","authors":"Sinmanus Vimonpatranon, Sydney K Mika, Alina P S Pang, Kawthar Machmach, Noemia S Lima, Sucheta Godbole, Chayada Sajjaweerawan, Elizabeth R Longtine, Amy R Henry, Farida Laboune, Ellie Metz, Nisakorn Ratnaratorn, Yuwadee Phuang-Ngern, Carlo Sacdalan, Julie A Ake, Barbara L Shacklett, Johan K Sandberg, Rungsun Rerknimitr, Nittaya Phanuphak, Sandhya Vasan, Daniel C Douek, Michael J Corley, Alexandra Schuetz, Dominic Paquin-Proulx","doi":"10.1016/j.mucimm.2026.100403","DOIUrl":"10.1016/j.mucimm.2026.100403","url":null,"abstract":"Mucosal-associated invariant T (MAIT) cells are an unconventional subset of T cells that respond to vitamin B2 metabolites from a range of bacteria and fungi. We have previously reported that peripheral MAIT cells are activated during acute HIV infection (AHI) in a manner associated with markers of microbial translocation. Here, we characterized peripheral and colonic MAIT cells from people with HIV (PWH) during AHI and after ART initiated during AHI or chronic HIV infection (CHI) and investigated their interplay with the colonic microbiome. During AHI, both peripheral and colonic MAIT cells were activated and showed evidence of proliferation. MAIT cell activation in blood and colon were unrelated to viral load and to each other, suggesting compartmentalized responses. Colonic CD4 MAIT cells were reduced and their reduction was associated with viral load, suggesting a direct viral effect. In vitro experiments confirmed that CD4 MAIT cells are susceptible to HIV-1 infection. Finally, changes in colonic microbiome composition were evident already during AHI and were associated with peripheral blood MAIT cell activation and effector maturation. Thus, these findings indicate that viral replication and colonic microbiome perturbation are associated with distinct, compartment-specific components of the MAIT cell response during AHI.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100403"},"PeriodicalIF":5.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13647192/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148930262","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}

引用次数: 0

Intestinal helminths skew dendritic cell development to counter the anti-helminth immune response. 肠道蠕虫扭曲树突状细胞发育以对抗抗蠕虫免疫反应。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-09-07 DOI: 10.1016/j.mucimm.2026.100402

Anna T Andrusaite, Ruby F White, Anna L L Heawood, Olivia Ridgewell, Daisy E Lints, Annika Frede, Anna Ahlback, Natalia L Wasowska, Holly C Webster, Kyle T Cunningham, Hiroki Yamaguchi, Sarwah Al-Khalidi, Molly Peel, Andrew Farthing, Kieran P Woolcock, Annabelle N Smith, Edward Roberts, Andrew S MacDonald, Allan Mcl Mowat, Rick M Maizels, Georgia Perona-Wright, Simon W F Milling

{"title":"Intestinal helminths skew dendritic cell development to counter the anti-helminth immune response.","authors":"Anna T Andrusaite, Ruby F White, Anna L L Heawood, Olivia Ridgewell, Daisy E Lints, Annika Frede, Anna Ahlback, Natalia L Wasowska, Holly C Webster, Kyle T Cunningham, Hiroki Yamaguchi, Sarwah Al-Khalidi, Molly Peel, Andrew Farthing, Kieran P Woolcock, Annabelle N Smith, Edward Roberts, Andrew S MacDonald, Allan Mcl Mowat, Rick M Maizels, Georgia Perona-Wright, Simon W F Milling","doi":"10.1016/j.mucimm.2026.100402","DOIUrl":"10.1016/j.mucimm.2026.100402","url":null,"abstract":"Intestinal dendritic cells (DC) orchestrate the adaptive immune response that balances protection against pathogens and tolerance towards harmless antigens. Yet, it remains largely unknown what molecular mechanisms underly this functional duality. Heligmosomoides polygyrus bakeri (Hpb) is a naturally occurring parasite in mice characterised by unique immune-evasion strategies that counter host protective immunity. Here, we utilised this unique infection environment to study mechanisms by which DC maintain the immune balance. In-depth characterisation of intestinal DC during Hpb infection revealed the emergence of distinct populations of DC that drive protective Th2 responses, versus others with immunoregulatory properties. We also identified that the skewing of intestinal DC towards immunoregulatory functions was due to TGFβ signalling via endogenous sources and by Hpb-produced TGFβ-mimic molecules. Thus, our results present a mechanistic explanation for Hpb's ability to modulate the adaptive immune system. Furthermore, these data offer an example of how heterogeneity within the DC compartment can determine the simultaneous generation of both pro- and anti-inflammatory immune responses.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100402"},"PeriodicalIF":5.5,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906835","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}

引用次数: 0

Zymosan-adjuvanted intranasal norovirus virus-like particle vaccine induces antiviral mucosal immune responses in infant mice. zymosan佐剂鼻内诺如病毒样颗粒疫苗诱导幼鼠黏膜抗病毒免疫反应。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-27 DOI: 10.1016/j.mucimm.2026.100401

Tomoya Tsuchihashi, Shiho Kurokawa, Shigeyuki Tamiya, Yutaka Nakamura, Rika Nakahashi-Ouchida, Naomi Sakon, Kohtaro Fujihashi, Yoshikazu Yuki, Hiroshi Kiyono, Shintaro Sato, Daisuke Tokuhara

{"title":"Zymosan-adjuvanted intranasal norovirus virus-like particle vaccine induces antiviral mucosal immune responses in infant mice.","authors":"Tomoya Tsuchihashi, Shiho Kurokawa, Shigeyuki Tamiya, Yutaka Nakamura, Rika Nakahashi-Ouchida, Naomi Sakon, Kohtaro Fujihashi, Yoshikazu Yuki, Hiroshi Kiyono, Shintaro Sato, Daisuke Tokuhara","doi":"10.1016/j.mucimm.2026.100401","DOIUrl":"10.1016/j.mucimm.2026.100401","url":null,"abstract":"Infants require repeated immunizations of injectable-type vaccines against different pathogens because their immune systems are weaker than those of adults. However, these injectable vaccines cause physical and psychological discomfort. Therefore, there is an urgent need to develop pain-free mucosal vaccines that are optimized for immunologically immature infants. Using an infant murine model, we examined the effectiveness of an intranasal norovirus virus-like-particle (VLP) vaccine with zymosan as an adjuvant. The intranasal immunization of infant mice with VLPs alone induced mucosal and systemic VLP-specific immune responses that were substantially weaker than those of adults. In contrast, infant mice administered a minimum dose of intranasal zymosan-adjuvanted VLP vaccine showed increased levels of intestinal and salivary VLP-specific IgA antibodies, as well as plasma VLP-specific IgG antibodies, at levels comparable to those in adults. Importantly, intestinal and salivary antibodies elicited by intranasal immunization with the zymosan-adjuvanted VLP vaccine effectively inhibited norovirus propagation in human-induced pluripotent stem cellderived intestinal epithelial cells. These findings suggest that the intranasal zymosan-adjuvanted norovirus VLP vaccine is an effective mucosal vaccine candidate for infants. It may help reduce the pain associated with injections and the number of immunizations infants required to achieve sufficient protective immunity against norovirus.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100401"},"PeriodicalIF":5.5,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148813559","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}

引用次数: 0

Efferent ductule epithelium orchestrates reproductive immune homeostasis under inflammatory stress. 传出小管上皮调控炎症应激下的生殖免疫稳态。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-13 DOI: 10.1016/j.mucimm.2026.100400

L Vinay, G Campolina-Silva, A D Andrade, P V Martini, J Q Bizzotto, S Ferrier-Tarin, I Allaeys, M Gentile, S Gastaldo, M P Scott-Boyer, A Droit, E Boilard, P Lupetti, E J R Silva, C Belleannée

{"title":"Efferent ductule epithelium orchestrates reproductive immune homeostasis under inflammatory stress.","authors":"L Vinay, G Campolina-Silva, A D Andrade, P V Martini, J Q Bizzotto, S Ferrier-Tarin, I Allaeys, M Gentile, S Gastaldo, M P Scott-Boyer, A Droit, E Boilard, P Lupetti, E J R Silva, C Belleannée","doi":"10.1016/j.mucimm.2026.100400","DOIUrl":"10.1016/j.mucimm.2026.100400","url":null,"abstract":"Immune dysregulation is increasingly recognized as a key contributor to male infertility, yet the role of the efferent ductules in reproductive immune homeostasis remains unexplored. Located between the immune-privileged testis and the epididymis, efferent ductules are essential for male fertility by reabsorbing over 90% of testicular fluid and maintaining sperm in suspension through the coordinated activity of reabsorptive primary ciliated cells (RPCCs) and multiciliated cells (MCCs). Using complementary in vivo and in vitro approaches, we investigated the contribution of efferent ductule epithelial cells to innate immunity. In a mouse model of lipopolysaccharide (LPS)-induced epididymitis, efferent ductules displayed significant interstitial neutrophil infiltration and abnormal sperm accumulation, indicating disrupted local homeostasis. Both mouse and human epithelial cells expressed Toll-like receptor 4 (TLR4), supporting a role in pathogen sensing. Transcriptomic analyses showed MCCs enriched in cilia-related genes, while RPCCs preferentially expressed genes involved in signaling and inflammation. To further explore epithelial immune function, we developed 3D organoid models recapitulating key features of efferent ductules. Upon LPS stimulation, these organoids mounted a robust innate immune response, secreting cytokines, chemokines, and growth factors, consistent with in vivo observations. Together, these findings identify efferent ductule epithelial cells as an upstream immunological checkpoint and establish organoids as a valuable model to study efferent ductule epithelial cells function in male reproductive health.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100400"},"PeriodicalIF":5.5,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148760788","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}

引用次数: 0

Delayed IL-17RA signaling in early life promotes type I interferon/CXCL10-dependent inhibition of pneumococcal clearance. 生命早期延迟的IL-17RA信号传导促进I型干扰素/ cxcl10依赖性肺炎球菌清除抑制。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-10 DOI: 10.1016/j.mucimm.2026.100399

Teniola Idowu, Daniel P Fecko, Hannes Eichner, Gavyn Chern Wei Bee, Kathryn A Knoop, Jeffrey N Weiser, Kristen L Lokken-Toyli

{"title":"Delayed IL-17RA signaling in early life promotes type I interferon/CXCL10-dependent inhibition of pneumococcal clearance.","authors":"Teniola Idowu, Daniel P Fecko, Hannes Eichner, Gavyn Chern Wei Bee, Kathryn A Knoop, Jeffrey N Weiser, Kristen L Lokken-Toyli","doi":"10.1016/j.mucimm.2026.100399","DOIUrl":"10.1016/j.mucimm.2026.100399","url":null,"abstract":"Early life is characterized by heightened susceptibility to respiratory pathogens, yet the immune mechanisms that predispose infants to infection remain poorly defined. Using an infant mouse model of Streptococcus pneumoniae (Spn) colonization, we identify an age-dependent delay in IL-17 A production that was associated with prolonged bacterial colonization in infant mice. Consistent with a critical role for this pathway, IL-17 receptor A (IL-17RA)-deficient infant mice exhibited persistent Spn colonization of the upper respiratory tract (URT). Transcriptomic profiling of the URT from Spn-colonized IL-17RA-deficient infant mice revealed an enrichment of antiviral responses compared to WT controls and included increased expression of the interferon-stimulated gene Cxcl10, a chemokine whose expression is positively associated with Spn carriage in humans. These results suggested that IL-17RA signaling constrains the interferon response during URT Spn colonization. WT infant mice exhibited progressively increased expression of Cxcl10 during Spn colonization and was dependent on type 1 interferon (IFNAR1) signaling and the pore forming bacterial toxin, pneumolysin. Genetic deletion of Ifnar1 or Cxcl10, including myeloid cell-specific deletion of Ifnar1, accelerated bacterial clearance in infant mice. In contrast, adult mice exhibited earlier induction of IL-17 A, minimal induction of Cxcl10 expression, and no alteration in bacterial clearance rates following Ifnar1 or Cxcl10 deficiency. Taken together, our results reveal a developmental window in which delayed IL-17 A production postpones the IL-17RA-dependent restraint of the type I interferon/CXCL10 axis, thereby prolonging pneumococcal carriage through impaired myeloid cell-mediated bacterial clearance.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100399"},"PeriodicalIF":5.5,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706932","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}

引用次数: 0

MAIT cells are associated with eosinophil presence and activation in the inflamed tissue of patients with eosinophilic esophagitis. MAIT细胞与嗜酸性粒细胞食管炎患者炎症组织中嗜酸性粒细胞的存在和激活有关。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-10 DOI: 10.1016/j.mucimm.2026.100398

Jan Devan, Vladimir Nosi, José Pedro Loureiro, Andreas Göldi, Lucia Mori, Gennaro De Libero, Petr Hruz

引用次数: 0

Beyond pathogen recognition: C-type lectin receptors in microbiota regulation 超越病原体识别：c型凝集素受体在微生物群调节中的作用。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-07-05 DOI: 10.1016/j.mucimm.2026.100376

Morgan Greenewood, June L. Round

引用次数: 0

Homeostatic and inflammatory functions of pulmonary GM-CSF 肺GM-CSF的稳态和炎症功能。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-07-07 DOI: 10.1016/j.mucimm.2026.100380

Antonie Lechner, Julia Gschwend, Christoph Schneider

引用次数: 0

CTL lymph node entrapment drives lymphopenia in severe influenza infection 在严重流感感染中，CTL淋巴结被困导致淋巴细胞减少。

IF 5.5 2区医学

Mucosal Immunology Pub Date : 2026-08-01 Epub Date: 2026-04-27 DOI: 10.1016/j.mucimm.2026.04.007

Aira F. Cabug, Nichollas E. Scott, Heran Zhang, Katherine Kedzierska, Linda M. Wakim

{"title":"CTL lymph node entrapment drives lymphopenia in severe influenza infection","authors":"Aira F. Cabug, Nichollas E. Scott, Heran Zhang, Katherine Kedzierska, Linda M. Wakim","doi":"10.1016/j.mucimm.2026.04.007","DOIUrl":"10.1016/j.mucimm.2026.04.007","url":null,"abstract":"<div><div>Influenza virus infection can result in outcomes ranging from moderate, self-limiting illness to severe, life-threatening disease. Although severe cases are frequently associated with CD8+ T cell lymphopenia, the underlying mechanisms driving this diminished T cell response remain poorly defined. Here, we investigated how severe influenza infection alters CD8+ T cell activation and trafficking. While CD8+ T cell priming was comparable between moderate and severe influenza infections, we found that during severe disease, effector CD8+ T cells were retained within the lung-draining lymph nodes (dLN). This entrapment was, in part, associated with a failure of effector CD8+ T cells to re-express the transcription factor KLF2 and its downstream target, the sphingosine-1-phosphate receptor S1PR1, a defect we show to be independent of both TGFβ and sustained TCR signalling. To evaluate the consequences of this impaired trafficking, we transferred effector CD8+ T cells directly into the bloodstream during severe influenza infection and found that intravenously delivered cells were rapidly and selectively eliminated upon entry into the inflamed lung. Our findings reveal that CD8+ T cell lymphopenia observed during severe influenza infection arises from two key mechanisms: sequestration of effector CD8+ T cells within the dLN and selective elimination of antigen-specific effectors within the lung tissue.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 4","pages":"Article 100346"},"PeriodicalIF":5.5,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776911","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}

引用次数: 0