{"title":"The biliary tree: A new frontier in mucosal immunology?","authors":"Guo Yin , Yasmina Chouik , Yawen Hao , Marlene Sophia Kohlhepp , Adrien Guillot","doi":"10.1016/j.mucimm.2026.04.006","DOIUrl":"10.1016/j.mucimm.2026.04.006","url":null,"abstract":"<div><div>Mucosal immunology traditionally applies to mucosal surfaces encountering microorganisms and environmental antigens, while the biliary tree is mostly regarded as a duct connecting the liver to the intestines. On the one hand, the biliary epithelium is considered a mucosal surface; on the other, it is not recognized as a mucosal immune epithelium. Nonetheless, emerging studies have robustly demonstrated its intricate roles in liver immunology and bile homeostasis, with direct consequences for the initiation and progression of liver diseases. Interestingly, emerging evidence suggests that bile ducts, and biliary epithelial cells in particular, display broad sensing capabilities and marked plasticity in their proteome and secretome, paralleling functions classically associated to mucosal immune epithelia. In this review, we discuss whether the bile ducts should be considered as part of the mucosal immunology system.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100345"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776906","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-03-30DOI: 10.1016/j.mucimm.2026.03.012
Jovana Maksimovic , Shivanthan Shanthikumar , George Howitt , Gunjan Dixit , Peter F Hickey , Casey Anttila , Daniel V. Brown , Liam Gubbels , Anne Senabouth , Daniela Amann-Zalcenstein , Joseph E. Powell , Sarath C. Ranganathan , Alicia Oshlack , Melanie R. Neeland
{"title":"Single-cell profiling of BAL in preschool cystic fibrosis reveals macrophage dysregulation and ivacaftor-modified inflammatory programs in the early life lung","authors":"Jovana Maksimovic , Shivanthan Shanthikumar , George Howitt , Gunjan Dixit , Peter F Hickey , Casey Anttila , Daniel V. Brown , Liam Gubbels , Anne Senabouth , Daniela Amann-Zalcenstein , Joseph E. Powell , Sarath C. Ranganathan , Alicia Oshlack , Melanie R. Neeland","doi":"10.1016/j.mucimm.2026.03.012","DOIUrl":"10.1016/j.mucimm.2026.03.012","url":null,"abstract":"<div><div>Aberrant inflammation and structural lung damage occurs early in life for people with cystic fibrosis (CF). Even in the era of CFTR modulators, anti-inflammatory therapy may still be needed to prevent establishment and lifelong consequences of bronchiectasis. In this study, we integrated transcriptome-wide single-cell RNA sequencing data and highly multiplexed surface protein expression to create the largest comprehensive paediatric lower airway atlas of >190,000 cells from 45 bronchoalveolar lavage (BAL) samples resulting in 43 immune and epithelial cell populations, all available for exploration on CELLxGENE. We then investigated inflammatory cell responses in children with CF to show widespread gene expression dysregulation of macrophage populations in the preschool CF lung. This included alterations in pathways associated with TNF and IFN signalling, cholesterol homeostasis, as well as pulmonary fibrosis, that were further altered by the early development of bronchiectasis. We showed that the CFTR modulator ivacaftor restores some of these macrophage-related functional deficits and reduces expression of pathways associated with neutrophil infiltration, however the modulator lumacaftor/ivacaftor did not result in any detectable changes in transcriptional response. This work represents a comprehensive, multi-omic single-cell analysis of BAL from preschool children and the results may inform the future development of anti-inflammatory therapy for children with CF.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100338"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147593375","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-02-19DOI: 10.1016/j.mucimm.2026.02.005
Mohammad H. Hasan , Ying Lin , Joselynn Wallace , Farha J. Mithila , Jessica Pacia , Geongoo Han , Khanhlinh Dinh , Chaoyu Ma , Nu Zhang , Lalit K. Beura
{"title":"Temporal Dissection of TGF-β signaling reveals differential impact during female reproductive mucosal CD8 resident memory T cell differentiation","authors":"Mohammad H. Hasan , Ying Lin , Joselynn Wallace , Farha J. Mithila , Jessica Pacia , Geongoo Han , Khanhlinh Dinh , Chaoyu Ma , Nu Zhang , Lalit K. Beura","doi":"10.1016/j.mucimm.2026.02.005","DOIUrl":"10.1016/j.mucimm.2026.02.005","url":null,"abstract":"<div><div>Resident memory CD8 T cell (TRM) development progresses through distinct stages beginning with activation of naive T cells into effectors in lymphoid organs, trafficking of effectors to target tissue via blood, and final TRM differentiation at the tissue of residence under the influence of the local microenvironment. The cytokine TGF-β has emerged as a central regulator of TRM formation, but how TGF-β modulates these distinct stages of TRM differentiation is not known. Combining an epithelial organoid system and genetic mouse models that limit TGF-β availability or restrict CD8 T cell-specific TGF-β signaling, here we probed the temporal requirement of TGF-β in the female reproductive tract (FRT) TRM formation. We found that restricting total or active TGF-β accessibility during naive T cell stage didn’t perturb CD8 T cells’ differentiation into TRM. However, abrogation of TGF-β signaling either during effector differentiation or early memory formation significantly reduced epithelial TRM differentiation. Even mature CD103+ CD8 TRM cells relied on TGF-β signaling for their continued persistence. Memory CD8 T cells generated in the absence of TGF-β signaling exhibit reduced proliferation after antigenic recall. Taken together, these suggest a stage-specific role of TGF-β in antiviral FRT mucosal TRM formation with implications for improving vaccination approaches.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100324"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146776469","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-03-09DOI: 10.1016/j.mucimm.2026.03.005
Yan Lu , Adrian Ilich , Ivana B. Ferreira , Rachael Y.M. Ryan , Darren A. Pickering , Sally Troy , Sharon M. Hoyte , Rebecca L. Johnston , Yide Wong , Alex Loukas , Severine Navarro
{"title":"Optimized hookworm-derived biologic, AIP-2NTQ48 restores mucosal tolerance and down-regulates colon cancer-associated gene expression in TNBS-induced colitis","authors":"Yan Lu , Adrian Ilich , Ivana B. Ferreira , Rachael Y.M. Ryan , Darren A. Pickering , Sally Troy , Sharon M. Hoyte , Rebecca L. Johnston , Yide Wong , Alex Loukas , Severine Navarro","doi":"10.1016/j.mucimm.2026.03.005","DOIUrl":"10.1016/j.mucimm.2026.03.005","url":null,"abstract":"<div><div>The development of treatments for ulcerative colitis (UC) has seen significant advancements over recent years, focusing on new drugs, innovative approaches, and a deeper understanding of the disease mechanisms. Few however have been able to restore natural tolerance. The hookworm-derived recombinant Anti-Inflammatory Protein (AIP)-2 has been previously shown to have promising pro-tolerogenic characteristics against asthma. Here we show that AIP-2 suppresses weight loss, colon damage, mucosal erosion and necrosis as well as the suppression of pro-inflammatory cytokines IL-6 and IFN-γ in a TNBS-induced model of UC. Following sequence optimization and efficacy comparison, we have generated the construct AIP-2<sub>NTQ48</sub> which contains the <em>N-</em>terminal sequence and an amino acid substitution (asparagine to glutamine) at position 48 to remove the <em>N</em>-glycan. AIP-2<sub>NTQ48</sub> significantly suppressed colon Th1/Th17 pathways and promoted regulatory T cells via TGF-β, IL-10 and ICOSL signaling in colon tissues. Transcriptomics analysis revealed differential expression of genes from the TNF receptor superfamily, TNF-α-induced genes and aldehyde dehydrogenase (ALDH) encoding enzymes which promoted tissue repair and the suppression of colorectal cancer-causing pathways. This suggests that AIP-2<sub>NTQ48</sub> promotes Treg/Th17 balance that could potentially offer a novel disease modifying therapeutic opportunity against UC.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100331"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147434328","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-03-14DOI: 10.1016/j.mucimm.2026.03.007
Gislane Almeida-Santos , Igor Santiago-Carvalho , Fabrício Moreira Almeida , Caio César Barbosa Bomfim , Juan Carlo Santos e Silva , Deborah Giovanna Cantarini , Camila Ramos Silva , Martha Simões Ribeiro , Rogério Silva do Nascimento , Bruna de Gois Macedo , Paulo Henrique Lisboa Raeder , Joaquim Teixeira-Xavier Junior , José Maria Alvarez , Mario Hiroyuki Hirata , Robson Coutinho-Silva , Simon C. Robson , Eduardo Pinheiro Amaral , Elena Lasunskaia , Maria Regina D’Império Lima
{"title":"CD39 regulates P2RX7-mediated lung necrotic lesions in severe experimental tuberculosis","authors":"Gislane Almeida-Santos , Igor Santiago-Carvalho , Fabrício Moreira Almeida , Caio César Barbosa Bomfim , Juan Carlo Santos e Silva , Deborah Giovanna Cantarini , Camila Ramos Silva , Martha Simões Ribeiro , Rogério Silva do Nascimento , Bruna de Gois Macedo , Paulo Henrique Lisboa Raeder , Joaquim Teixeira-Xavier Junior , José Maria Alvarez , Mario Hiroyuki Hirata , Robson Coutinho-Silva , Simon C. Robson , Eduardo Pinheiro Amaral , Elena Lasunskaia , Maria Regina D’Império Lima","doi":"10.1016/j.mucimm.2026.03.007","DOIUrl":"10.1016/j.mucimm.2026.03.007","url":null,"abstract":"<div><div>Infection with <em>Mycobacterium tuberculosis</em> can cause diverse lesions, such as necrotic pneumonia, which can contribute to tuberculosis progression and transmission between individuals. Despite advances in understanding the role of ATP-gated P2RX7 ion channels in the development of severe forms of the disease, the regulation of this important signaling pathway remains unclear. Herein, we show that the ectonucleotidase CD39 plays an essential regulatory role in tuberculosis progression by preventing lung tissue damage, bacterial dissemination, and excessive inflammatory responses. Mechanistically, through its enzymatic activity on the cellular surface, CD39 protects infected macrophages from undergoing necrotic death mediated by P2RX7 activation. Cell-intrinsic CD39 expression also hinders the establishment of other myeloid cells, such as neutrophils, in the infected lung. We proposed that, by protecting infected macrophages from P2RX7-mediated cell death and bacterial dissemination in the lung tissue, CD39 prevents the development of necrotic lesions. Altogether, these findings uncover a significant role for CD39 as an essential component of the molecular regulation underlying the development of severe tuberculosis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100333"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147468731","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-04-12DOI: 10.1016/j.mucimm.2026.04.005
Lennart Heepmann , Wiebke Hartmann , Lara Linnemann , Sara Dörken , Birte Viebrock , Zane Orinska , Thomas Jacobs , Henry J. McSorley , Minka Breloer
{"title":"CD160-competent ILC2 are crucial for the ejection of intestinal helminths by the innate immune system","authors":"Lennart Heepmann , Wiebke Hartmann , Lara Linnemann , Sara Dörken , Birte Viebrock , Zane Orinska , Thomas Jacobs , Henry J. McSorley , Minka Breloer","doi":"10.1016/j.mucimm.2026.04.005","DOIUrl":"10.1016/j.mucimm.2026.04.005","url":null,"abstract":"<div><div>1.6 billion people are currently infected with parasitic worms. Group 2 innate lymphoid cells (ILC2) play a central role in promoting the protective type 2 immunity against these parasites. Here we show that a subpopulation of intestinal ILC2 express the immune checkpoint molecule CD160 in mice infected with the parasitic nematode <em>Strongyloides ratti.</em> CD160<sup>+</sup> ILC2 represented a distinct ST2<sup>-</sup>IL-17RB<sup>+</sup>Ki-67<sup>+</sup> subset that expanded <em>in vivo</em> during <em>S. ratti</em> infection. By contrast, CD160<sup>-</sup> ILC2 were ST2<sup>+</sup>IL-17RB<sup>-</sup>Ki-67<sup>-</sup> and represented the dominant producers of type 2 cytokines. Upon <em>in vitro</em> stimulation, sorted CD160<sup>+</sup> ILC2 progressively lost CD160 expression and acquired cytokine-producing capacity. While CD160-competent RAG KO mice efficiently controlled <em>S. ratti</em> infection with less than 1% of the infective dose remaining by day 10 post-infection, CD160-deficient RAG KO mice failed to expand intestinal ILC2, failed to activate mucosal mast cells and retained high intestinal worm burden for nearly 100 days. Adoptive transfer of CD160-competent ILC2 into <em>S. ratti</em>-infected CD160-deficient RAG KO mice partially restored mast cell activation and reduced intestinal worm burden by 50%. Collectively, these findings identify CD160 expression as a critical checkpoint in the development and expansion of fully functional ILC2 required for effective immunity against intestinal helminth infection.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100344"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675087","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-02-21DOI: 10.1016/j.mucimm.2026.02.004
Emma Ruysseveldt , Tine Wils , Daan Rodiers , Toon Ieven , Janne Goossens , Ellen Dilissen , Jonathan Cremer , Dominique M.A. Bullens , Katleen Martens , Brecht Steelant , Peter W. Hellings
{"title":"Interaction between airway basal cells, mast cells and type 2 immunity contributes to epithelial barrier dysfunction in allergic rhinitis","authors":"Emma Ruysseveldt , Tine Wils , Daan Rodiers , Toon Ieven , Janne Goossens , Ellen Dilissen , Jonathan Cremer , Dominique M.A. Bullens , Katleen Martens , Brecht Steelant , Peter W. Hellings","doi":"10.1016/j.mucimm.2026.02.004","DOIUrl":"10.1016/j.mucimm.2026.02.004","url":null,"abstract":"<div><div>Basal cell dysfunction contributes to the pathophysiology of chronic inflammatory airway disorders and is linked to persistent epithelial barrier defects. Epithelial integrity dysfunction, basal cell hyperplasia and metaplasia have been described in allergic rhinitis (AR). However, it remains unclear how basal cell progenitor functions are regulated and if basal cells contribute to type 2 inflammatory responses. Here, we report on the proinflammatory and sensory role of basal cells in AR. Using primary nasal basal cells from controls and AR patients, we demonstrate that Der p1 induces basal cell cytokine (IL-6) and chemokine (CXCL1, CXCL6, CXCL8, SCF) expression and/or release via PAR2, suggesting a role for basal cells as environmental sensors and inflammatory regulators. Using nasal biopsies, we show that mast cells are attracted to the epithelium in AR, likely via basal cell-derived SCF, and induce basal cell chemokine (CCL26, CXCL1, CXCL6, SCF) release via histamine and tryptase <em>in vitro</em>. Finally, histamine, IL-4 and IL-13 impair primary nasal basal cell proliferation, mobility, barrier formation, and differentiation in <em>in vitro</em> cellular assays, illustrating basal cell dysfunction in AR.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100323"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276919","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-03-05DOI: 10.1016/j.mucimm.2026.03.002
Max Augustin , Lea Picard , Dominic Rauschning , Elisabeth Zenev , Elisabeth Pracht , Ute Sandaradura de Silva , Ferdinand Heyn , Melanie Ball , Isabella Rostocki , Gerhard Herzog , Franz Ludwig Dumoulin , Ting-Huee Lin , Harald Kirschner , Sophia Petschnak , Eva Heger , Eloísa Felipe Fumero , Marie-Christine Albert , Henning Walczak , Michael Stingl , Manuela Födinger , Clara Lehmann
{"title":"Persistent Gut-Immune Axis dysregulation in long-term Post-COVID Syndrome: Insights from a prospective, observational, cross-sectional case-control study","authors":"Max Augustin , Lea Picard , Dominic Rauschning , Elisabeth Zenev , Elisabeth Pracht , Ute Sandaradura de Silva , Ferdinand Heyn , Melanie Ball , Isabella Rostocki , Gerhard Herzog , Franz Ludwig Dumoulin , Ting-Huee Lin , Harald Kirschner , Sophia Petschnak , Eva Heger , Eloísa Felipe Fumero , Marie-Christine Albert , Henning Walczak , Michael Stingl , Manuela Födinger , Clara Lehmann","doi":"10.1016/j.mucimm.2026.03.002","DOIUrl":"10.1016/j.mucimm.2026.03.002","url":null,"abstract":"<div><div>Post-COVID syndrome (PCS) is a complex condition that can emerge after recovery from SARS-CoV-2 infection, even in young, healthy individuals with mild acute illness. While the underlying mechanisms remain unclear, viral persistence and immune dysregulation are considered key contributors. This study investigates whether the persistence of viral proteins in gut-associated lymphoid tissue (GALT) is linked to PCS and how it may influence immune cell populations in the terminal ileum (TI). Peripheral blood (PB) and TI biopsies were obtained 15 to 22 months after acute SARS-CoV-2 infection from 43 SARS-CoV-2 convalescent patients (20 with (PCS<sup>+</sup>) and 23 without PCS symptoms (PCS<sup>−</sup>)). Mononuclear cells were isolated from PB and TI for flow cytometric and histological analysis. PCS<sup>+</sup> individuals exhibited a distinct immune profile characterized by increased mast cell activity, and elevated zonulin levels, indicating compromised gut barrier function alongside with elevated SARS-CoV-2 nucleocapsid protein expression in the TI. Additional findings included expansion of plasmacytoid dendritic cells, alterations in NK cell subsets, and higher proportions of central memory T-cells with low PD-1 expression in TI. Elevated MMP-9 levels further indicated localized gut inflammation and tissue remodeling. These results highlight the gut-immune interface as potential driver of PCS and support therapeutic strategies targeting viral persistence and intestinal immune homeostasis.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100328"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147372913","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-04-07DOI: 10.1016/j.mucimm.2026.03.006
Caio César Barbosa Bomfim , Hugo Génin , Jammy Mariotton , Isabelle Matias , Daniela Cota , Nicolas Barry Delongchamps , Marc Zerbib , Morgane Bomsel , Yonatan Ganor
{"title":"Cannabidiol prevents mucosal HIV-1 transmission by targeting Langerhans cells, dendritic cells, macrophages and T-cells","authors":"Caio César Barbosa Bomfim , Hugo Génin , Jammy Mariotton , Isabelle Matias , Daniela Cota , Nicolas Barry Delongchamps , Marc Zerbib , Morgane Bomsel , Yonatan Ganor","doi":"10.1016/j.mucimm.2026.03.006","DOIUrl":"10.1016/j.mucimm.2026.03.006","url":null,"abstract":"<div><div>HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4<sup>+</sup> T-cells or macrophages, and indirect viral transfer to CD4<sup>+</sup> T-cells from Langerhans cells (LCs) or dendritic cells (DCs). LCs-mediated HIV-1 transfer is inhibited by the neuropeptide calcitonin gene-related peptide (CGRP), due to upstream activation in LCs of the transient receptor potential vanilloid 1 (TRPV1) ion channel. Herein, we investigated the potential anti-HIV-1<!--> <!-->roles of cannabidiol (CBD), the non-psychoactive compound in marijuana, which has well-described immunosuppressive functions and principally activates TRPV1 over its cognate CB1 and CB2 receptors. We found that via TRPV1 activation, CBD<!--> <!-->inhibits<!--> <em>in-vitro<!--> </em>infection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4<sup>+</sup> T-cells HIV-1 direct infection or upon viral transfer from LCs<!--> <!-->and DCs. Moreover, inhibition of macrophages infection and LCs-mediated HIV-1 transfer involves secreted CGRP.<!--> <!-->Importantly, CBD also blocks early events of HIV-1 transmission <em>ex-vivo</em> in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4<sup>+</sup> T-cells infection. Altogether, CBD inhibits infection of all HIV-1 cellular targets, and commercial CBD products might be repositioned as novel HIV-1 pre-exposure prophylaxis, namely ‘CBD PrEP’.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100332"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147776930","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}
Mucosal ImmunologyPub Date : 2026-06-01Epub Date: 2026-02-21DOI: 10.1016/j.mucimm.2026.02.006
Consuelo Micheli , Ana Rita Oliveira , Beatriz Millán , Marcos Cardoso , Marta Araújo , Cláudio Duarte-Oliveira , Ana Mendes-Frias , Ricardo Silvestre , Cristina Cunha , Agostinho Carvalho , Fernando Rodrigues , Manuel Vilanova , África González-Fernández , António G. Castro , Egídio Torrado
{"title":"Alveolar macrophages shape tuberculosis susceptibility by delaying protective immunity","authors":"Consuelo Micheli , Ana Rita Oliveira , Beatriz Millán , Marcos Cardoso , Marta Araújo , Cláudio Duarte-Oliveira , Ana Mendes-Frias , Ricardo Silvestre , Cristina Cunha , Agostinho Carvalho , Fernando Rodrigues , Manuel Vilanova , África González-Fernández , António G. Castro , Egídio Torrado","doi":"10.1016/j.mucimm.2026.02.006","DOIUrl":"10.1016/j.mucimm.2026.02.006","url":null,"abstract":"<div><div>Effective control of <em>Mycobacterium tuberculosis</em> (Mtb) infection requires timely activation and accumulation of CD4<sup>+</sup> T cells in the lungs, yet the factors delaying this response remain unclear. Here we show that alveolar macrophages (AMs) delay CD4<sup>+</sup> T cell priming by retaining Mtb within the alveolar lumen, limiting other myeloid cells access to the bacteria. This defect is more pronounced in susceptible C3HeB/FeJ mice than in C57BL/6 mice and arises from reduced IL-1β and GM-CSF production, which impair the migration of AMs to the lung parenchyma. Targeting AMs accelerates the activation of the adaptive immune response but fails to promote bacterial control over the chronic phase of infection due to neutrophils interference on CD4<sup>+</sup> T cell function. Crucially, sequential depletion of AMs and neutrophils restores CD4<sup>+</sup> T cell function and enhances infection control. These findings uncover a novel bottleneck in tuberculosis immunity and suggest that targeting AMs may accelerate adaptive immunity but overcoming local inflammatory constraints may be necessary to sustain infection control.</div></div>","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":"19 3","pages":"Article 100325"},"PeriodicalIF":7.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147276853","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}
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