Mucosal Immunology最新文献

Candidalysin promotes fungal-specific Th17 CD4 T cell differentiation and protective systemic immunogenicity. 念珠菌素促进真菌特异性Th17 CD4 T细胞分化和保护性全身免疫原性。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-05-07 DOI: 10.1016/j.mucimm.2026.100348

Ngan N M Nguyen, Alexander E Brady, David B Haslam, Corey Frazer, Giang Pham, Richard J Bennett, Sing Sing Way

{"title":"Candidalysin promotes fungal-specific Th17 CD4 T cell differentiation and protective systemic immunogenicity.","authors":"Ngan N M Nguyen, Alexander E Brady, David B Haslam, Corey Frazer, Giang Pham, Richard J Bennett, Sing Sing Way","doi":"10.1016/j.mucimm.2026.100348","DOIUrl":"https://doi.org/10.1016/j.mucimm.2026.100348","url":null,"abstract":"Commensal microbes can cause invasive infection but can also stimulate protective immune responses as exemplified by the gut pathobiont Candida albicans. This species primes systemic Th17 immunogenicity which protects against disseminated infection, and yet the fungal determinants driving protection remain uncertain. Here we show an essential role for the cytolytic toxin candidalysin for C. albicans colonization-induced systemic Th17 immunogenicity and protection against invasive infection. Mice intestinally colonized with candidalysin-deficient cells show reduced accumulation of CD4 T cells with defined fungal specificity, despite similar intestinal colonization levels to wildtype C. albicans cells. Fungal-specific RORγt + CD4 T cells are particularly reduced together with their production of IL17A and IL17F cytokines, whereas expression of transcription factors and production of cytokines representative of other helper T cell lineages are unaffected. Protection against fungemia conferred by colonization with wildtype C. albicans is absent from mice colonized with candidalysin-deficient cells as shown by increased fungal pathogen burden and reduced survival after intravenous infection. These results establish the necessity for candidalysin for priming Th17 fungal-specific adaptive immune cells and highlight paradoxical protective roles for this fungal virulence factor for promoting host defense against invasive systemic disease.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100348"},"PeriodicalIF":7.6,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147864210","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

Cytokine networks driving eosinophil functional heterogeneity. 细胞因子网络驱动嗜酸性粒细胞功能异质性。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-05-01 DOI: 10.1016/j.mucimm.2026.100347

James I King, Isabelle C Arnold

{"title":"Cytokine networks driving eosinophil functional heterogeneity.","authors":"James I King, Isabelle C Arnold","doi":"10.1016/j.mucimm.2026.100347","DOIUrl":"10.1016/j.mucimm.2026.100347","url":null,"abstract":"Eosinophils have traditionally been viewed as terminally differentiated type 2 effector cells involved in anti-helminth immunity and allergic inflammation. Recent advances in single-cell transcriptomics have refined this view, revealing substantial developmental and functional heterogeneity across tissues and inflammatory settings. Eosinophil development in the bone marrow is controlled by lineage-defining transcription factors and by cytokines such as IL-5, IL-3, GM-CSF and IL-33, which regulate progenitor expansion, maturation, mobilization and survival. After entering tissues, eosinophils integrate local cytokine, stromal, epithelial, microbial and metabolic signals to acquire context-dependent activation states. In this review, we summarize core developmental programs of eosinophils and examine how cytokine networks shape their responses across type 1, type 2 and type 17 immunity. We discuss evidence that eosinophils contribute not only to classical type 2 responses, but also to antimicrobial, cytotoxic, immunoregulatory and tissue-remodeling programs in non-type 2 settings, positioning them as highly plastic effectors with broad roles in host defense, tissue homeostasis and disease.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100347"},"PeriodicalIF":7.6,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147817894","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

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 7.6 2区医学

Mucosal Immunology Pub 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":"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.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":"100346"},"PeriodicalIF":7.6,"publicationDate":"2026-04-27","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The biliary tree: A new frontier in mucosal immunology? 胆道树：粘膜免疫学的新前沿？

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-19 DOI: 10.1016/j.mucimm.2026.04.006

Guo Yin, Yasmina Chouik, Yawen Hao, Marlene Sophia Kohlhepp, Adrien Guillot

引用次数: 0

CD160-competent ILC2 are crucial for the ejection of intestinal helminths by the innate immune system. cd160表达的ILC2对于先天免疫系统排出肠道蠕虫至关重要。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-12 DOI: 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":"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 Strongyloides ratti. CD160+ ILC2 represented a distinct ST2-IL-17RB+Ki-67+ subset that expanded in vivo during S. ratti infection. By contrast, CD160- ILC2 were ST2+IL-17RB-Ki-67- and represented the dominant producers of type 2 cytokines. Upon in vitro stimulation, sorted CD160+ ILC2 progressively lost CD160 expression and acquired cytokine-producing capacity. While CD160-competent RAG KO mice efficiently controlled S. ratti 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 S. ratti-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.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-12","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}

引用次数: 0

Eomes fate-labeling reveals a subset of Eomes^lo NK cells that exhibits an ILC1-like phenotype. Eomes命运标记揭示了Eomeslo NK细胞的一个亚群，其表现出ilc1样表型。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-09 DOI: 10.1016/j.mucimm.2026.04.003

Vladislava Stokic-Trtica, Johannes Steffen, Xuemei Gao, Henning Düsedau, Sotiria Boulekou, Sebastian J Arnold, Antigoni Triantafyllopoulou, Chiara Romagnani, Andreas Diefenbach, Yakup Tanriver, Ildiko R Dunay, Christoph S N Klose

{"title":"Eomes fate-labeling reveals a subset of Eomeslo NK cells that exhibits an ILC1-like phenotype.","authors":"Vladislava Stokic-Trtica, Johannes Steffen, Xuemei Gao, Henning Düsedau, Sotiria Boulekou, Sebastian J Arnold, Antigoni Triantafyllopoulou, Chiara Romagnani, Andreas Diefenbach, Yakup Tanriver, Ildiko R Dunay, Christoph S N Klose","doi":"10.1016/j.mucimm.2026.04.003","DOIUrl":"https://doi.org/10.1016/j.mucimm.2026.04.003","url":null,"abstract":"Innate lymphoid cells (ILCs) are distinct lineages defined by lineage-specifying transcription factors that drive their differentiation and effector programs. Despite being stable lineages, ILC plasticity has been reported. Plasticity is characterized by downregulation of the transcription factor that specifies the current ILC lineage, followed by upregulation of the transcription factor and surface markers that determine the phenotype of the ILC lineage it is acquiring. Even though NK cells rely on the lineage-specifying transcription factor Eomes, an unusual phenotype characterized by ILC1 marker expression was reported in the salivary glands and during Toxoplasma gondii infection. However, it remains unclear whether this reflects true ILC plasticity or simply phenotypic changes. Using a dual-reporter system that allows simultaneous detection of live expression and fate-labeling of Eomes, we observed downregulation of this lineage-specifying transcription factor in NK cells (Eomeslo cells) and upregulation of ILC1 markers in the salivary gland and multiple organs during Toxoplasma gondii infection, including organs that otherwise promote NK cell fate. While Eomeslo cells adopted an ILC1-like phenotype, they differentiated in the absence of Hobit, a pivotal transcription factor of ILC1s, distinguishing them from the ILC1 lineage. Therefore, our data demonstrate that NK cells can adopt an Eomeslo ILC1-like fate, even in the blood and secondary lymphoid organs, complementing previous findings on ILC2 and ILC3 plasticity towards the ILC1 lineage.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662957","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

Epithelial barrier DUOX2 serves as early immune defense in intestinal pathogen control. 上皮屏障DUOX2在肠道病原体控制中起早期免疫防御作用。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-09 DOI: 10.1016/j.mucimm.2026.04.004

Maurice O'Mara, Suisheng Zhang, Claire Fergus, Vincent P Kelly, Ulla G Knaus

{"title":"Epithelial barrier DUOX2 serves as early immune defense in intestinal pathogen control.","authors":"Maurice O'Mara, Suisheng Zhang, Claire Fergus, Vincent P Kelly, Ulla G Knaus","doi":"10.1016/j.mucimm.2026.04.004","DOIUrl":"10.1016/j.mucimm.2026.04.004","url":null,"abstract":"Epithelial barriers constitute the first line of immune defense, preventing pathogen adherence, growth and entry through physical and chemical mechanisms. Essential to chemical defense are reactive oxygen species, usually provided by the phagocyte NADPH oxidase. DUOX2, a related oxidase, functions as sensor of the gut environment, and its dysregulation has been associated with inflammatory bowel disease. Here, we combine cell-based approaches with newly developed transgenic mice to explore how altering epithelial DUOX2 activity shapes host responses to intestinal bacteria including IBD-associated pathogens and to chemical colitis inducers. Although the pathogenic mechanisms of these bacteria differ, each triggered DUOX2 recruitment and transient H2O2 bursts in the vicinity of the pathogen during early, but not late, stages of infection. In vivo, epithelial DUOX2 acted as universal immune defense system without inducing or perpetuating intestinal inflammation. Our findings show that epithelial DUOX2 chemically undermines pathogen-induced niches, decreasing bacterial virulence and strengthening the barrier.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147662937","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

The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity. Nox2 NADPH氧化酶调节口腔中性粒细胞炎症。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-08 DOI: 10.1016/j.mucimm.2026.04.002

Shunying Jin, Richa Singhal, Jianzhu Luo, Yasmine H Higgins, Kelley N Cooper, Marina Terekhova, Katherine A Carey, Audrey F Duff, Maxim N Artyomov, Venkatakrishna R Jala, Rachel A Idol, Michael T Bailey, Mary C Dinauer, Richard J Lamont, Juhi Bagaitkar

{"title":"The Nox2 NADPH oxidase regulates neutrophilic inflammation in the oral cavity.","authors":"Shunying Jin, Richa Singhal, Jianzhu Luo, Yasmine H Higgins, Kelley N Cooper, Marina Terekhova, Katherine A Carey, Audrey F Duff, Maxim N Artyomov, Venkatakrishna R Jala, Rachel A Idol, Michael T Bailey, Mary C Dinauer, Richard J Lamont, Juhi Bagaitkar","doi":"10.1016/j.mucimm.2026.04.002","DOIUrl":"10.1016/j.mucimm.2026.04.002","url":null,"abstract":"The leukocyte NADPH oxidase 2 (Nox2) is an important regulator of inflammatory responses, independent of its antimicrobial activity. Inactivating mutations in NOX2 cause chronic granulomatous disease (CGD), a severe immunodeficiency associated with recurrent infections and dysregulated neutrophilic inflammation. Recurrent oral ulcers, stomatitis, gingivitis, and other inflammatory issues affecting the oral mucosa have been observed in patients with CGD; however, the underlying mechanisms are not known. Here, we present evidence that the extensive inflammatory destruction of oral mucosal tissues observed in Nox2-deficient or CybbKO mice was not caused by impaired antimicrobial surveillance against oral pathobionts but instead resulted from a cell-intrinsic dysregulation of neutrophil inflammatory responses. Transcriptional and cellular profiling of oral tissues isolated from wild-type and CybbKO mice showed a dominant neutrophil signature, which was accompanied by a significant upregulation of several bone-resorbing, tissue-degrading inflammatory cytokines and a reduced expression of nuclear factor erythroid 2-related factor 2 (Nrf2) regulated genes. Mechanistically, hyperinflammatory responses were mitigated by restoring Nrf2 transcriptional activity using a synthetic agonist. Thus, our studies show that the Nox2 oxidase and derivative reactive oxygen species are crucial for balanced neutrophil recruitment and cell-intrinsic regulation of their inflammatory responses within oral tissues in an Nrf2-dependent manner.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147654638","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

Cannabidiol prevents mucosal HIV-1 transmission by targeting Langerhans cells, dendritic cells, macrophages and T-cells. 大麻二酚通过靶向朗格汉斯细胞、树突状细胞、巨噬细胞和t细胞来阻止粘膜HIV-1传播。

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-07 DOI: 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":"https://doi.org/10.1016/j.mucimm.2026.03.006","url":null,"abstract":"HIV-1 transmission depends on the structure and immune cell composition of mucosal epithelia. Transmission mechanisms involve direct infection of CD4+ T-cells or macrophages, and indirect viral transfer to CD4+ 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-1roles 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, CBDinhibitsin-vitroinfection of mucosal HIV-1 cellular targets. Specifically, CBD inhibits macrophages HIV-1 direct infection, and CD4+ T-cells HIV-1 direct infection or upon viral transfer from LCsand 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 ex-vivo in human inner foreskin tissues, namely formation of epidermal LC-T-cell conjugates and resulting CD4+ 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'.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-07","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}

引用次数: 0

Differential effects of SARS-CoV-2-targeted infection of ATII, club cells, and macrophages on lung immunopathology and antiviral responses. sars - cov -2靶向ATII、俱乐部细胞和巨噬细胞感染对肺免疫病理和抗病毒反应的差异影响

IF 7.6 2区医学

Mucosal Immunology Pub Date : 2026-04-06 DOI: 10.1016/j.mucimm.2026.04.001

Austin W Todd, Sergey A Shein, Anna A Korchagina, Vasily A Kudinov, Brianna N Faz, Ramya S Barre, Raehum Paik, Emma C Collins, Kizil A Yusoof, Ishana Khetarpal, Korri S Weldon, Zhao Lai, Dias Kurmashev, Jordi B Torelles, Elizabeth A Leadbetter, Yan Xiang, Yidong Chen, Luis Martinez-Sobrido, Ekaterina Koroleva, Alexei V Tumanov

{"title":"Differential effects of SARS-CoV-2-targeted infection of ATII, club cells, and macrophages on lung immunopathology and antiviral responses.","authors":"Austin W Todd, Sergey A Shein, Anna A Korchagina, Vasily A Kudinov, Brianna N Faz, Ramya S Barre, Raehum Paik, Emma C Collins, Kizil A Yusoof, Ishana Khetarpal, Korri S Weldon, Zhao Lai, Dias Kurmashev, Jordi B Torelles, Elizabeth A Leadbetter, Yan Xiang, Yidong Chen, Luis Martinez-Sobrido, Ekaterina Koroleva, Alexei V Tumanov","doi":"10.1016/j.mucimm.2026.04.001","DOIUrl":"10.1016/j.mucimm.2026.04.001","url":null,"abstract":"The specific contributions of lung epithelial and immune cells to SARS-CoV-2-induced immunopathology and antiviral responses remain unclear. To address this, we generated mouse models with inducible expression of human angiotensin-converting enzyme 2 (hACE2) in specific lung cell types. Infection of mice expressing hACE2 on club cells triggered early type I interferon responses, limited viral replication, and caused transient, mild lung pathology. In contrast, hACE2-driven infection of type II alveolar epithelial cells (ATIIs) resulted in higher viral loads and moderate lung damage, accompanied by expansion of interstitial macrophages, virus-specific CD8+ T cell responses, and production of anti-SARS-CoV-2 IgG. Additionally, infection of mice expressing hACE2 on ATIIs increased CD11c+ CD8+ effector T cells and proinflammatory cytokines in the lungs, including IFN-γ, CXCL9, and CXCL10. However, neutralization of CXCL9 and CXCL10 exacerbated disease severity. Moreover, infection of mice with hACE2 targeted to ATIIs and macrophages led to severe lung injury, increased viral burden, enhanced T-cell and neutrophil infiltration, higher IgG responses, and sustained lung pathology. In contrast, hACE2 expression limited to endothelial cells was insufficient to promote SARS-CoV-2 replication in the lung or cause pathology. Together, these findings demonstrate that ACE2-driven infection of ATIIs, club cells, and macrophages plays distinct but cooperative roles in driving SARS-CoV-2-induced lung immunopathology and antiviral immunity.","PeriodicalId":18877,"journal":{"name":"Mucosal Immunology","volume":" ","pages":""},"PeriodicalIF":7.6,"publicationDate":"2026-04-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639341","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