Démoulins, Thomas; Baron, Marie-Laurence; Gauchat, Dominique; Kettaf, Nadia; Reed, Steve James; Charpentier, Tania; Kalinke, Ulrich; Lamarre, Alain 
ORCID: https://orcid.org/0000-0002-7913-871X; Ahmed, Rafi; Sekaly, Rafick-Pierre; Sarkar, Surojit et Kalia, Vandana
(2022).
Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection
Virology
, vol. 567
.
pp. 77-86.
DOI: 10.1016/j.virol.2021.12.007.
Résumé
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.
| Type de document: | Article |
|---|---|
| Mots-clés libres: | Acute; CD8 T cells; Chronic; Thymic atrophy; Thymopoiesis; Type-I interferons; Viral infection |
| Centre: | Centre INRS-Institut Armand Frappier |
| Date de dépôt: | 23 juin 2022 02:24 |
| Dernière modification: | 23 juin 2022 02:24 |
| URI: | https://espace.inrs.ca/id/eprint/12326 |
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