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Barrier immune memory is programmed by intestinal epithelial cell presentation of cytosol-delivered bacterial antigens.

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Τίτλος: Barrier immune memory is programmed by intestinal epithelial cell presentation of cytosol-delivered bacterial antigens.
Συγγραφείς: Wilson CG; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. cgwilson@uabmc.edu.; Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA. cgwilson@uabmc.edu., Acharya MP; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Karsch L; Institute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Duck LW; Department of Medicine, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Twumasi-Ankrah N; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Wang Y; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Shen H; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Frey BF; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA.; Medical Scientist Training Program, University of Alabama at Birmingham, Birmingham, AL, USA., McKee AR; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Oza VH; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Harbour SN; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Nagaoka-Kamata Y; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Singer JR; Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA., Hatton RD; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Moffitt J; Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA., Gunzer M; Institute for Experimental Immunology and Imaging, University Hospital Essen, University Duisburg-Essen, Essen, Germany., Zindl CL; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA., Weaver CT; Department of Pathology, Heersink School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA. cweaver@uabmc.edu.
Πηγή: Nature immunology [Nat Immunol] 2026 Oct; Vol. 27 (10), pp. 2117-2133. Date of Electronic Publication: 2026 Sep 30.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Nature America Inc Country of Publication: United States NLM ID: 100941354 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1529-2916 (Electronic) Linking ISSN: 15292908 NLM ISO Abbreviation: Nat Immunol Subsets: MEDLINE
Imprint Name(s): Original Publication: New York, NY : Nature America Inc. c2000-
Ιατρικοί όροι (MeSH): Antigens, Bacterial*/immunology , Citrobacter rodentium*/immunology , Antigen Presentation*/immunology , Intestinal Mucosa*/immunology , Intestinal Mucosa*/microbiology , CD4-Positive T-Lymphocytes*/immunology , Enterobacteriaceae Infections*/immunology , Enterobacteriaceae Infections*/microbiology , Epithelial Cells*/immunology , Memory T Cells*/immunology , Immunologic Memory*, Cytosol/immunology ; Cytosol/metabolism ; Antigen-Presenting Cells/immunology ; Animals ; Mice ; Mice, Inbred C57BL
Περίληψη: Antigen compartmentalization is known to influence CD4 and CD8 T cell recognition but its impact on immune responses to different antigens expressed by the same pathogen is poorly understood. By tracking the clonal CD4 T cell response to a single epitope shuttled between different virulence proteins of Citrobacter rodentium, we found that response magnitude and quality depended on antigen localization. Antigens retained within bacteria elicited limited responses, whereas antigens injected into colonocyte cytosol through a type III secretion system generated robust mucosal CD4 T cell responses and promoted formation of epithelial-resident memory T cells. This process required direct presentation by infected epithelial cells. Single-cell transcriptomic analyses revealed that sustained, bidirectional communication between epithelial cells and T cells was essential to elicit both barrier-protective functions and transcriptional programs favoring tissue residency over central memory differentiation. These findings identify nonprofessional antigen-presenting cells as key regulators of CD4 T cell memory fate.
(© 2026. The Author(s).)
Competing Interests: Competing interests: The authors declare no competing interests.
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Grant Information: F30 DK135345 United States DK NIDDK NIH HHS; R37 AI169864 United States AI NIAID NIH HHS; T32 AI007051 United States AI NIAID NIH HHS; U01 AI163063 United States AI NIAID NIH HHS
Substance Nomenclature: 0 (Antigens, Bacterial)
Entry Date(s): Date Created: 20260930 Date Completed: 20261002 Latest Revision: 20261004
Update Code: 20261004
PubMed Central ID: PMC13630577
DOI: 10.1038/s41590-026-02656-7
PMID: 42816586
Βάση Δεδομένων: MEDLINE
Περιγραφή
ISSN:1529-2916
DOI:10.1038/s41590-026-02656-7