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Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection

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 . p. 77-86. DOI: 10.1016/j.virol.2021.12.007.

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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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