Type I interferons and MAVS signaling are necessary for tissue resident memory CD8+ T cell responses to RSV infection
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Published version
Author(s)
Type
Journal Article
Abstract
Respiratory syncytial virus (RSV) can cause bronchiolitis and viral pneumonia in young children and the elderly. Lack of vaccines and recurrence of RSV infection indicate the difficulty in eliciting protective memory immune responses. Tissue resident memory T cells (TRM) can confer protection from pathogen re-infection and, in human experimental RSV infection, the presence of lung CD8+ TRM cells correlates with a better outcome. However, the requirements for generating and maintaining lung TRM cells during RSV infection are not fully understood. Here, we use mouse models to assess the impact of innate immune response determinants in the generation and subsequent expansion of the TRM cell pool during RSV infection. We show that CD8+ TRM cells expand independently from systemic CD8+ T cells after RSV re-infection. Re-infected MAVS and MyD88/TRIF deficient mice, lacking key components involved in innate immune recognition of RSV and induction of type I interferons (IFN-α/β), display impaired expansion of CD8+ TRM cells and reduction in antigen specific production of granzyme B and IFN-γ. IFN-α treatment of MAVS deficient mice during primary RSV infection restored TRM cell expansion upon re-challenge but failed to recover TRM cell functionality. Our data reveal how innate immunity, including the axis controlling type I IFN induction, instructs and regulates CD8+ TRM cell responses to RSV infection, suggesting possible mechanisms for therapeutic intervention.
Date Issued
2022-02-02
Date Acceptance
2022-01-28
ISSN
1553-7366
Publisher
Public Library of Science (PLoS)
Journal / Book Title
PLoS Pathogens
Volume
18
Issue
2
Copyright Statement
© 2022 Varese et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Sponsor
Medical Research Council (MRC)
Rosetrees Trust
Rosetrees Trust
National Heart and Lung Institute Foundation
Wellcome Trust
Cancer Research UK
Wellcome Trust
Rosetrees Trust
European Respiratory Society and the Asociación Latinoamericana de Tórax
Medical Research Council (MRC)
Grant Number
G0800311
M370
A442
Michelle Goritzka
109058/Z/15/Z
27217
109058/Z/15/Z
M370-F1
LTRF 201901-00546
MR/V000659/1
Subjects
Virology
0605 Microbiology
1107 Immunology
1108 Medical Microbiology
Publication Status
Published
Article Number
ARTN e1010272