Mucosal Immunology最新文献_第3页

Editing B cells at the IGHA2 gene position provides alternative route to therapeutic IgA production 在IGHA2基因位置编辑B细胞为治疗性IgA生产提供了另一种途径。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-10-01 DOI: 10.1016/j.mucimm.2025.06.001

Marine Cahen , Jenny Léonard , Ophélie Dézé , Laurent Deleurme , Maiwenn Pineau , Anne-Laure Tanguy , Stéphane Paul , Jérome Moreaux , Grégory Noël , Natsuko Ueda , Yannic Danger , Michel Cogné

{"title":"Editing B cells at the IGHA2 gene position provides alternative route to therapeutic IgA production","authors":"Marine Cahen , Jenny Léonard , Ophélie Dézé , Laurent Deleurme , Maiwenn Pineau , Anne-Laure Tanguy , Stéphane Paul , Jérome Moreaux , Grégory Noël , Natsuko Ueda , Yannic Danger , Michel Cogné","doi":"10.1016/j.mucimm.2025.06.001","DOIUrl":"10.1016/j.mucimm.2025.06.001","url":null,"abstract":"<div><div>As professional and long-lived immunoglobulin (Ig) producers, B cells represent attractive candidates for adoptive immunotherapy and their highly expressed Ig heavy (IgH) chain locus is ideal for editing. Each of its constant genes, expressed after class switch recombination (CSR), affords an attractive platform where an adoptive Ig variable domain would acquire IgM, IgG, IgE or IgA class-specific functions. In particular, IgA plays a unique role in mucosal immunity but has remained excluded from therapeutic applicability due to unfavorable chemistry, manufacturing, and control (CMC) issues. To test whether these barriers could be overcome by producing IgA in vivo rather than in vitro, we edited the human B cell-specific IGHA2 gene and found it to be a suitable platform for inserting gene cassettes for expression in B cells. Targeted deletions can also induce CSR to IgA2, while, by combining IgA2 CSR with the insertion of a linked VH and a complete light chain, we have replaced the endogenous Ig chains with a customized full-size but single-chain IgA carrying an adoptive antigen specificity.</div><div>Taken together, we show that IGHA2-editing of B cells could provide a novel avenue to B-cell targeted delivery of therapeutic IgA, overcoming the problems that have so far excluded IgA from clinical use.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"18 5","pages":"Pages 1027-1035"},"PeriodicalIF":7.6,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144248855","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

Corrigendum to "Lung-resident memory Th2 cells regulate pulmonary cryptococcosis by inducing type-II granuloma formation" [Mucosal Immunol. 18(3) (2025) 631-642]. “肺常驻记忆Th2细胞通过诱导ii型肉芽肿形成调节肺隐球菌病”的更正[粘膜免疫，18(3)(2025)631-642]。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-30 DOI: 10.1016/j.mucimm.2025.09.006

Keigo Ueno, Akiko Nagamori, Nahoko Oniyama Honkyu, Kyung J Kwon-Chung, Yoshitsugu Miyazaki

引用次数: 0

Novel loss-of-function intronic mutation in ELF4 is associated with intestinal autoinflammation. ELF4中新的功能缺失内含子突变与肠道自身炎症有关。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-24 DOI: 10.1016/j.mucimm.2025.09.007

Chunyang Tian, Xiaoqi Ye, Shanshan Xiong, Gayatree Mohapatra, Sinan Lin, Ziyin Ye, Siyun Huang, Xin Yu, Baili Chen, Yao He, Yinglian Xiao, Zhirong Zeng, Yijun Zhu, Minhu Chen, Danping Zheng

{"title":"Novel loss-of-function intronic mutation in ELF4 is associated with intestinal autoinflammation.","authors":"Chunyang Tian, Xiaoqi Ye, Shanshan Xiong, Gayatree Mohapatra, Sinan Lin, Ziyin Ye, Siyun Huang, Xin Yu, Baili Chen, Yao He, Yinglian Xiao, Zhirong Zeng, Yijun Zhu, Minhu Chen, Danping Zheng","doi":"10.1016/j.mucimm.2025.09.007","DOIUrl":"10.1016/j.mucimm.2025.09.007","url":null,"abstract":"Monogenic errors of immunity can present with inflammatory bowel disease (IBD)-like enteropathy. We describe an adolescent with IBD- and Behçet's-like phenotype, resulting from an intronic, loss of function mutation (c.248-7G > A) in ELF4, an X-linked transcription factor executing multiple biological functions. The mutation causes abnormal splicing and decreased mRNA expression and impairs ELF4 protein expression in the blood and colon. Functionally, the mutation results in loss of ELF4 transcriptional activity, and transcriptionally induces auto-inflammatory responses in the patient's peripheral blood mononuclear cells, which promote secretion of the pro-inflammatory cytokine interleukin-6 upon lipopolysaccharide stimulation. Single-cell transcriptional profiling of inflamed colonic biopsy specimens from the patient delineates a comprehensive landscape of mucosal innate and adaptive immune dysregulation. This analysis not only uncovers inflammatory signatures reminiscent of Crohn's disease but also demonstrates heightened angiogenic chemokine responses and enhanced chemotactic activity in innate immune cells. These results demonstrate that a new ELF4 loss-of-function intronic mutation predisposes to an intestinal autoinflammatory disorder.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145176042","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

Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children. 鼻病毒C15感染诱导气道上皮细胞重塑和强烈的炎症反应：对儿童气道阻塞的潜在影响

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-18 DOI: 10.1016/j.mucimm.2025.09.002

Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson

{"title":"Rhinovirus C15 infection induces airway epithelial cell remodeling and robust inflammatory responses: Potential implications for airway obstruction in children.","authors":"Yiran Li, Shilpi Singh, Hannah L Briggs, Jordan E Kreger, Alex L Sliwicki, Emily L Eberhardt, Shiuhyang Kuo, Jessica A Czapla, J Kelley Bentley, Heidi R Flori, Amjad Horani, Steven L Brody, Marc B Hershenson","doi":"10.1016/j.mucimm.2025.09.002","DOIUrl":"10.1016/j.mucimm.2025.09.002","url":null,"abstract":"Despite recognition of rhinovirus-C (RV-C) as a cause of severe respiratory exacerbations, little is known about the pathogenesis of RV-C infections. We infected mucociliary-differentiated primary tracheobronchial epithelial cells with RV-C15 or RV-A16. Initial RNASeq data showed that, compared to RV-A16, RV-C15 decreased expression of genes related to ciliary function while increasing expression of genes associated with mucus secretion and inflammation. Using different airway epithelial cell isolates, we confirmed greater reduction in DNAI2 and FOXJ1 (regulates production of motile cilia) and increased FOXA3 (regulates mucin -related gene expression) after RV-C15 infection compared to RV-A16. Similarly, nasal swab samples from children with RV-C but not RV-A infections showed significantly decreased DNAI2 and FOXJ1 mRNA compared to controls. While both RV-C15 and RV-A16 infection of airway epithelial cells increased mRNA expression and secretion of MUC5AC, RV-C15 induced greater airway surface liquid thickness, as measured by FITC-dextran staining. DAPT, a Notch inhibitor, reversed the effects of RV-C15 on DNAI2, FOXJ1 and FOXA3 expression. RV-C15 induced loss of α-acetyl tubulin, extrusion of airway epithelial cells, dissociation of ZO-1 from tight junctions, reduced ciliary beat frequency and decreased epithelial cell transepithelial electrical resistance. Finally, protein abundance of pro-inflammatory cytokines in cell supernatants and nasal samples also tended to be higher after RV-C infection. We conclude that RV-C causes significant disruptions in airway epithelial cell ciliary function which may lead to airway obstruction. Such disruptions may play a role in the severity of RV-C respiratory tract infections.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102837","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

IgA-dependent cell phagocytosis of HIV-infected cells elicits cross-presentation to CD8+T cells and immune memory in effector monocytes. hiv感染细胞的iga依赖性细胞吞噬引起CD8+T细胞的交叉呈递和效应单核细胞的免疫记忆。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-18 DOI: 10.1016/j.mucimm.2025.09.004

Andrea Cottignies-Calamarte, Annouk Dauvilliers, Lucie Adoux, Benjamin Saint-Pierre, Franck Letourneur, Sylvain Cardinaud, Daniela Tudor, Morgane Bomsel

{"title":"IgA-dependent cell phagocytosis of HIV-infected cells elicits cross-presentation to CD8+T cells and immune memory in effector monocytes.","authors":"Andrea Cottignies-Calamarte, Annouk Dauvilliers, Lucie Adoux, Benjamin Saint-Pierre, Franck Letourneur, Sylvain Cardinaud, Daniela Tudor, Morgane Bomsel","doi":"10.1016/j.mucimm.2025.09.004","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.09.004","url":null,"abstract":"Mucosal IgA antibodies are the first defence against mucosal infections. Besides targeting specific antigens by their Fab-region, IgA also mediates antiviral functions via their Fc-domain, allowing infected cells destruction by antibody-dependent cellular phagocytosis (ADCP). Passive immunisation with anti-HIV-1 IgG protected Non-Human Primates in a CD8+ T cell-dependent manner, a process likely involving ADCP. Here, we unravel the consequences of ADCP of HIV-1-infected cells mediated by anti-HIV envelope IgA compared to IgG. We found that IgA-mediated ADCP, not IgG, drives viral antigen cross-presentation to HIV-1-specific cytotoxic CD8+ T cells. IgA effector function reprogrammed ADCP effector monocytes into activated macrophages exhibiting a mixed pro- and anti-inflammatory profile combined with increased pro-inflammatory chemokines. IgA-mediated ADCP sensitizes monocytes to respond to a novel bacterial challenge by secreting IL-6 and TNFα, indicative of acquired trained immunity. Altogether, these data establish a bridge between humoral and cellular immunity that could be exploited in HIV preventive strategies.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145102839","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

Akkermansia muciniphila ameliorates Salmonella-induced colitis and intestinal fibrosis. 嗜粘杆菌改善沙门氏菌诱导的结肠炎和肠道纤维化。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-15 DOI: 10.1016/j.mucimm.2025.09.005

Abdulhadi Suwandi, Soeren Ocvirk, Alibek Galeev, Marijana Basic, Reza R A Naderi, Daphne Dior Tientcheu Tchokoafi, Anika Sander, Christiane Ring, Diana Ring, Gopala Nishanth, Katrin Künnemann, Dirk Schlüter, Andre Bleich, Michael Blaut, Bärbel Stecher, Gunnar Loh, Guntram A Grassl

{"title":"Akkermansia muciniphila ameliorates Salmonella-induced colitis and intestinal fibrosis.","authors":"Abdulhadi Suwandi, Soeren Ocvirk, Alibek Galeev, Marijana Basic, Reza R A Naderi, Daphne Dior Tientcheu Tchokoafi, Anika Sander, Christiane Ring, Diana Ring, Gopala Nishanth, Katrin Künnemann, Dirk Schlüter, Andre Bleich, Michael Blaut, Bärbel Stecher, Gunnar Loh, Guntram A Grassl","doi":"10.1016/j.mucimm.2025.09.005","DOIUrl":"10.1016/j.mucimm.2025.09.005","url":null,"abstract":"Salmonella enterica serovar Typhimurium is a food-borne pathogen and a major cause of gastroenteritis in humans. The intestinal microbiota provides colonization resistance to enteric pathogens such as S. Typhimurium. Akkermansia muciniphila is an anaerobic bacterium commonly found in the intestinal tract of humans and other mammals and specializes in the degradation of mucin. To study the role of A. muciniphila in affecting the outcome of S. Typhimurium colonization and pathology, we used gnotobiotic mice colonized with a defined simplified human (SIHUMI) or mouse (OMM11) intestinal microbiota and infected them with the attenuated S. Typhimurium ΔaroA strain. By comparing SIHUMI and OMM11 mice to mice additionally colonized with A. muciniphila, we demonstrate that the presence of A. muciniphila leads to a decrease in intestinal Salmonella colonization. In addition, Salmonella-induced colitis is significantly reduced in the presence of A. muciniphila including improved histopathological changes as well as decreased levels of inflammatory cytokines. Furthermore, we demonstrate that viable A. muciniphila inhibit adhesion of Salmonella to the intestinal epithelium in vivo as well as to differentiated, polarized HT29-MTX-E12 epithelial cells. These data indicate that A. muciniphila plays an important role in mediating protection from S. Typhimurium colitis by inhibiting adhesion of Salmonella to the intestinal epithelium.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145081159","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

Neutrophil ADAM10 promotes migration and inflammation in ARDS by modulating adhesion and chemokine signaling. 中性粒细胞ADAM10通过调节粘附和趋化因子信号传导促进ARDS的迁移和炎症。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-12 DOI: 10.1016/j.mucimm.2025.09.003

Anika Fuhr, Meike Goerlich, Anna Biedritzky, Carolin Kleinmaier, Ka-Lin Heck-Swain, Jutta Gamper-Tsigaras, Kristian-Christos Ngamsri, Franziska Konrad, Michael Koeppen

{"title":"Neutrophil ADAM10 promotes migration and inflammation in ARDS by modulating adhesion and chemokine signaling.","authors":"Anika Fuhr, Meike Goerlich, Anna Biedritzky, Carolin Kleinmaier, Ka-Lin Heck-Swain, Jutta Gamper-Tsigaras, Kristian-Christos Ngamsri, Franziska Konrad, Michael Koeppen","doi":"10.1016/j.mucimm.2025.09.003","DOIUrl":"10.1016/j.mucimm.2025.09.003","url":null,"abstract":"Acute respiratory distress syndrome (ARDS) is characterized by excessive neutrophil recruitment, endothelial barrier dysfunction, and persistent inflammation. A Disintegrin and Metalloproteinase 10 (ADAM10) regulates leukocyte trafficking by cleaving adhesion molecules such as VE-cadherin and JAM-A, but its role in neutrophil-driven lung injury remains unclear. We investigated whether neutrophil-derived ADAM10 modulates neutrophil adhesion, migration, and pulmonary inflammation in a murine model of ARDS and assessed the effects of systemic ADAM10 inhibition. Using a neutrophil-specific ADAM10 knockout mouse model (ADAM10loxP/loxPCatchup-Cre+) and pharmacological ADAM10 inhibition, we evaluated neutrophil recruitment, endothelial permeability, and adhesion molecule expression in lipopolysaccharide (LPS)-induced lung inflammation. Flow cytometry, immunofluorescence, and enzyme-linked immunosorbent assay (ELISA) were used to assess neutrophil migration, activation, and cytokine release. In vitro adhesion and transmigration assays were performed with human endothelial and epithelial monolayers using freshly isolated human neutrophils. Neutrophil-specific ADAM10 deletion did not affect endothelial permeability but reduced neutrophil recruitment into the alveolar space, associated with decreased CXCL1 and CXCL2/3 secretion and increased CD44 surface expression. ADAM10 inhibition enhanced adhesion but impaired transmigration, mirroring genetic deletion. Systemic inhibition also suppressed neutrophil activation and inflammatory cytokine release. Neutrophil ADAM10 promotes neutrophil migration and inflammation in ARDS by modulating chemokine signaling and adhesion molecule expression. Systemic ADAM10 inhibition reduces neutrophil infiltration and inflammatory cytokine production, suggesting ADAM10 as a potential therapeutic target to mitigate neutrophil-driven lung injury.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145065350","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

Single cell map of the adult female mouse urethra reveals epithelial and stromal macrophages with distinct functional identities. 成年雌性小鼠尿道单细胞图谱揭示了具有不同功能特征的上皮和间质巨噬细胞。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-09-02 DOI: 10.1016/j.mucimm.2025.09.001

Jasmine, Mrinal Samtiya, Richelle Rodrigues, Aparna Mandal, T T Kavya, Anubhuti Anushree, John T Lafin, Chad M Vezina, Douglas W Strand, Diya Binoy Joseph

{"title":"Single cell map of the adult female mouse urethra reveals epithelial and stromal macrophages with distinct functional identities.","authors":"Jasmine, Mrinal Samtiya, Richelle Rodrigues, Aparna Mandal, T T Kavya, Anubhuti Anushree, John T Lafin, Chad M Vezina, Douglas W Strand, Diya Binoy Joseph","doi":"10.1016/j.mucimm.2025.09.001","DOIUrl":"10.1016/j.mucimm.2025.09.001","url":null,"abstract":"Epithelial linings at mucosal sites act in concert with resident immune cells to direct host defense. The epithelial lining of the urethra is an understudied mucosal barrier with emerging roles in antimicrobial defense during urinary tract infections. Here, we present a comprehensive cellular atlas of the adult female mouse urethra, focusing on epithelial and resident immune cells. Single cell RNA-sequencing revealed two distinct macrophage populations compartmentalized within the epithelium and stroma. Epithelial-associated macrophages display a highly dendritic morphology and populate the urethral lining in increasing numbers over the course of development. Epithelial-associated macrophages express Cx3cr1, MHCII genes, Cd74 and Aif1/Iba-1, representing an activated macrophage type (Mac-Activated) enriched for pathways involved in antigen presentation and the inflammatory response. In contrast, stromal macrophages express the scavenging receptors Mrc1/Cd206, Lyve1, Cd163 and Mgl2/Cd301b and display a signature enriched for endocytic function (Mac-Endocytic), vasculature development and tissue homeostasis. We identified epithelial cells in the urethral lining and associated glands expressing the monocyte chemoattractant genes Cx3cl1 and Cxcl17. Chemoattractant gene expression in the urethral epithelium follows a proximal-distal gradient which correlates with the increasing density of epithelial-associated macrophages expressing the receptor Cx3cr1 along the proximal-distal axis of the urethra. The study delineates spatially compartmentalized macrophage subsets in the urethra and implicates epithelial-derived chemokines in the establishment of macrophage positioning and functional specialization along the urethral axis.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7618168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145001018","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

CREB-mediated sensing of bacterial membrane vesicles unveils a conserved host defense pathway. creb介导的细菌膜囊泡传感揭示了一个保守的宿主防御途径。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-27 DOI: 10.1016/j.mucimm.2025.08.007

Saifei Wang, Bohan Qi, Chunyu Du, Peng Ma, Yao Zhang, Shuxin Chen, E Tian, Hansong Deng

{"title":"CREB-mediated sensing of bacterial membrane vesicles unveils a conserved host defense pathway.","authors":"Saifei Wang, Bohan Qi, Chunyu Du, Peng Ma, Yao Zhang, Shuxin Chen, E Tian, Hansong Deng","doi":"10.1016/j.mucimm.2025.08.007","DOIUrl":"10.1016/j.mucimm.2025.08.007","url":null,"abstract":"Bacterial membrane vesicles (MVs) are critical mediators of virulence factor delivery and intercellular communication, yet the mechanisms by which hosts detect and respond to these vesicles remain poorly characterized. Through transcriptional profiling, we found that MVs derived from the non-lethal pathogenic Erwinia carotovora carotovora 15 (Ecc15) robustly induce reactive oxygen species (ROS) production and systemically upregulate Jon genes-a family of immune-related genes-in the Drosophila intestine 24 h post-infection. Strikingly, these effects contrast with transcriptional changes observed upon gut-specific overexpression of CRTC, the coactivator of the conserved transcription factor cAMP response element-binding protein (CREB). Intriguingly, ingestion of OMVs from Ecc15 or from the Gram-positive bacterium Lactobacillus plantarum (L.plantarum) significantly suppresses CREB activity in enterocytes (ECs). Fractionation experiments revealed that proteinaceous components within bacterial MVs inhibited CREB activity by reducing apical Ca2+ levels in ECs. Mechanistically, the CRTC/CREB cascade promoted gut microbial load by transcriptionally repressing PGRP-SC2-dependent amidase activity, a pathway independent of the canonical Relish/Imd signaling axis. Furthermore, OMVs from E. coli (BL21) also potently suppressed expression of pro-inflammatory factors, such as IL-6 and CXCL10 in NIH3T3 by blocking the activity of CREB. Collectively, these findings demonstrated that CREB play a conserved role on sense bacterial MVs and trigger anti-infection defenses in both Drosophila and mammalian systems, unveiling a novel paradigm in host-microbe communication.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961696","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

Expansion of genital Tregs reduces neutrophil influx and maintains mucosal barrier integrity during inflammatory bacteria challenge. 生殖器Tregs的扩张减少中性粒细胞内流，并在炎症细菌攻击期间维持粘膜屏障的完整性。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2025-08-21 DOI: 10.1016/j.mucimm.2025.08.006

Faisal Nuhu, Marina Costa-Fujishima, Christina Gavino, Aloysious Ssemaganda, Melika Verdipanah, Naima Jahan, Thomas Murooka, Lyle R McKinnon

{"title":"Expansion of genital Tregs reduces neutrophil influx and maintains mucosal barrier integrity during inflammatory bacteria challenge.","authors":"Faisal Nuhu, Marina Costa-Fujishima, Christina Gavino, Aloysious Ssemaganda, Melika Verdipanah, Naima Jahan, Thomas Murooka, Lyle R McKinnon","doi":"10.1016/j.mucimm.2025.08.006","DOIUrl":"https://doi.org/10.1016/j.mucimm.2025.08.006","url":null,"abstract":"Genital inflammation is associated with increased HIV risk. We previously found that endocervical Tregs correlated with decreased genital inflammation and reduced HIV target cells. IL-2 induces Tregs, and efforts to potentiate its regulatory activities clinically are ongoing. In this study, intraperitoneal administration of IL-2 conjugated to IL-2mAb clone JES6-1A12 (IL2C-trimeric) in estrous-synchronized female FoxP3GFP mice selectively expanded Tregs in the lower female genital tract, with limited effects on non-Treg cells. IL2C-trimeric increased the expression of GITR on Tregs, and most Tregs expressed tissue residency markers. IL2C-trimeric pre-treatment prevented neutrophil influx during vaginal challenge with both nonoxynol-9 (N-9) and Mobiluncus mulieris, but maintenance of E-cadherin expression and barrier integrity was only observed for M. mulieris and not N-9. Depletion of FoxP3+Tregs reversed the protective effects of IL2C-trimeric. Thus, induction of Tregs could be a potential strategy to regulate genital inflammation, reduce HIV acquisition risk, and improve reproductive health outcomes in women.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144961829","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