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, Steven James; Charpentier, Tania; Kalinke, Ulrich; Lamarre, Alain; Ahmed, Rafi; Sékaly, Rafick-Pierre; Sarkar, Surojit; Kalia, Vandana (2022). Induction of thymic atrophy and loss of thymic output by type-I interferons during chronic viral infection. Virology, 567, pp. 77-86. Elsevier 10.1016/j.virol.2021.12.007

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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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Virology and Immunology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Démoulins, Thomas Paul Rémi

Subjects:

500 Science > 570 Life sciences; biology
500 Science > 590 Animals (Zoology)
600 Technology > 610 Medicine & health
600 Technology > 630 Agriculture

ISSN:

1096-0341

Publisher:

Elsevier

Language:

English

Submitter:

Pamela Schumacher

Date Deposited:

15 Aug 2022 09:12

Last Modified:

05 Dec 2022 16:22

Publisher DOI:

10.1016/j.virol.2021.12.007

PubMed ID:

35032866

BORIS DOI:

10.48350/171915

URI:

https://boris.unibe.ch/id/eprint/171915

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