Tissue-Resident-Memory CD8+ T Cells Bridge Innate Immune Responses in Neighboring Epithelial Cells to Control Human Genital Herpes

Tissue-resident-memory T cells (TRM) populate the body’s barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser c...

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Vydáno v:	Frontiers in immunology Ročník 12; s. 735643
Hlavní autoři:	Peng, Tao, Phasouk, Khamsone, Sodroski, Catherine N., Sun, Sijie, Hwangbo, Yon, Layton, Erik D., Jin, Lei, Klock, Alexis, Diem, Kurt, Magaret, Amalia S., Jing, Lichen, Laing, Kerry, Li, Alvason, Huang, Meei-Li, Mertens, Max, Johnston, Christine, Jerome, Keith R., Koelle, David M., Wald, Anna, Knipe, David M., Corey, Lawrence, Zhu, Jia
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland Frontiers Media S.A 06.09.2021
Témata:	Adaptive Immunity - genetics Adult Aged Antigens, Viral - immunology CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism CD8-Positive T-Lymphocytes - virology cell-intrinsic immunity Cells, Cultured Epithelial Cells - immunology Epithelial Cells - metabolism Epithelial Cells - virology Female Gene Expression Profiling Herpes Genitalis - genetics Herpes Genitalis - immunology Herpes Genitalis - metabolism Herpes Genitalis - virology Herpesvirus 2, Human - immunology Herpesvirus 2, Human - pathogenicity Host-Pathogen Interactions human genital herpes Humans IFI16 restriction factor Immunity, Innate - genetics Immunologic Memory Immunology innate antiviral response Interferon-gamma - genetics Interferon-gamma - metabolism Male Memory T Cells - immunology Memory T Cells - metabolism Memory T Cells - virology Middle Aged Phenotype Skin - immunology Skin - metabolism Skin - virology tissue microenvironment tissue-resident-memory T cells (TRM) Transcriptome innate antiviral response cell-intrinsic immunity human genital herpes tissue-resident-memory T cells (TRM) IFI16 restriction factor tissue microenvironment
ISSN:	1664-3224, 1664-3224
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Shrnutí:	Tissue-resident-memory T cells (TRM) populate the body’s barrier surfaces, functioning as frontline responders against reencountered pathogens. Understanding of the mechanisms by which CD8TRM achieve effective immune protection remains incomplete in a naturally recurring human disease. Using laser capture microdissection and transcriptional profiling, we investigate the impact of CD8TRM on the tissue microenvironment in skin biopsies sequentially obtained from a clinical cohort of diverse disease expression during herpes simplex virus 2 (HSV-2) reactivation. Epithelial cells neighboring CD8TRM display elevated and widespread innate and cell-intrinsic antiviral signature expression, largely related to IFNG expression. Detailed evaluation via T-cell receptor reconstruction confirms that CD8TRM recognize viral-infected cells at the specific HSV-2 peptide/HLA level. The hierarchical pattern of core IFN- γ signature expression is well-conserved in normal human skin across various anatomic sites, while elevation of IFI16, TRIM 22, IFITM2, IFITM3, MX1, MX2, STAT1, IRF7, ISG15, IFI44, CXCL10 and CCL5 expression is associated with HSV-2-affected asymptomatic tissue. In primary human cells, IFN- γ pretreatment reduces gene transcription at the immediate-early stage of virus lifecycle, enhances IFI16 restriction of wild-type HSV-2 replication and renders favorable kinetics for host protection. Thus, the adaptive immune response through antigen-specific recognition instructs innate and cell-intrinsic antiviral machinery to control herpes reactivation, a reversal of the canonical thinking of innate activating adaptive immunity in primary infection. Communication from CD8TRM to surrounding epithelial cells to activate broad innate resistance might be critical in restraining various viral diseases.
Bibliografie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Harvey Michael Friedman, University of Pennsylvania, United States; Jieun Oh, Korea Advanced Institute of Science and Technology, South Korea; Jason Schenkel, Brigham and Women’s Hospital and Harvard Medical School, United States Edited by: Haina Shin, Washington University in St. Louis, United States This article was submitted to Immunological Memory, a section of the journal Frontiers in Immunology
ISSN:	1664-3224 1664-3224
DOI:	10.3389/fimmu.2021.735643