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Prompt Antiviral Action of Pulmonary CD8+ TRM Cells Is Mediated by Rapid IFN-γ Induction and Its Downstream ISGs in the Lung

Authors :
Lang Jiang
Lu Liu
Miaomiao Zhang
Linxia Zhang
Cuisong Zhu
Qian He
Lilin Ye
Chen Zhao
Zejun Li
Jianqing Xu
Xiaoyan Zhang
Source :
Frontiers in Immunology, Vol 13 (2022)
Publication Year :
2022
Publisher :
Frontiers Media S.A., 2022.

Abstract

Growing lines of evidence supported the importance of CD8+ lung tissue resident memory T (TRM) cells in protection against respiratory viruses, exemplified by influenza A virus. However, the underlying in vivo mechanism remains largely undetermined. Here, we used mouse infection models to dissect in vivo cross-protective activity of lung CD8+ TRM cells. By simultaneously interrogating transcriptional dynamics in lung CD8+ TRM cells and surrounding tissues during the early course of infection, we demonstrated that lung CD8+ TRM cells react to antigen re-exposure within hours, manifested by IFN-γ upregulation, and a tissue-wide interferon-stimulated gene (ISG) program is subsequently elicited. Using antibody-mediated IFN-γ neutralization and IFN-γ receptor knockout mice, we could show that the induction of several important antiviral ISGs required IFN-γ signaling, so did the suppression of key inflammatory cytokines. Interestingly, there were also examples of ISGs unaffected in the absence of IFN-γ activity. Collectively, focusing on in situ characterization of lung CD8+ TRM cells during very early stage of infection, a critical period of host antiviral defense that has been poorly investigated, our studies highlight that these cells, once triggered by antigen re-exposure, are programmed to produce IFN-γ expeditiously to promote a lung-wide antiviral response for effective virus control.

Details

Language :
English
ISSN :
16643224
Volume :
13
Database :
Directory of Open Access Journals
Journal :
Frontiers in Immunology
Publication Type :
Academic Journal
Accession number :
edsdoj.7bc52463a6cb4c8aa4de5f11587720ea
Document Type :
article
Full Text :
https://doi.org/10.3389/fimmu.2022.839455