Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection
Publisher DOI
PubMed ID
35032866
Abstract
Type-I interferon (IFN-I) signals exert a critical role in disease progression during viral infections. However, the immunomodulatory mechanisms by which IFN-I dictates disease outcomes remain to be fully defined. Here we report that IFN-I signals mediate thymic atrophy in viral infections, with more severe and prolonged loss of thymic output and unique kinetics and subtypes of IFN-α/β expression in chronic infection compared to acute infection. Loss of thymic output was linked to inhibition of early stages of thymopoiesis (DN1-DN2 transition, and DN3 proliferation) and pronounced apoptosis during the late DP stage. Notably, infection-associated thymic defects were largely abrogated upon ablation of IFNαβR and partially mitigated in the absence of CD8 T cells, thus implicating direct as well as indirect effects of IFN-I on thymocytes. These findings provide mechanistic underpinnings for immunotherapeutic strategies targeting IFN-1 signals to manipulate disease outcomes during chronic infections and cancers.
Date Issued
2022-02
Publication Type
Article
Language(s)
en
Author(s)
Baron, Marie-Laurence | |
Gauchat, Dominique | |
Kettaf, Nadia | |
Reed, Steven James | |
Charpentier, Tania | |
Kalinke, Ulrich | |
Lamarre, Alain | |
Ahmed, Rafi | |
Sékaly, Rafick-Pierre | |
Sarkar, Surojit | |
Kalia, Vandana |
Additional Credits
Journal
Virology
Publisher
Elsevier
ISSN
1096-0341
Access(Rights)
restricted