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Type I interferon-induced beta-catenin promotes hematopoietic stem cell activation in persistent viral infection in mice

Nguyen, Trieu Hai; Kwarteng, Edward Owusu; Laulhe, Xavier; Chartrand, Karine; Lamarre, Alain ORCID logoORCID: https://orcid.org/0000-0002-7913-871X et Heinonen, Krista M. ORCID logoORCID: https://orcid.org/0000-0002-2410-4432 (2021). Type I interferon-induced beta-catenin promotes hematopoietic stem cell activation in persistent viral infection in mice In: AAI Anual Meeting, May 10–15, 2021, Virtual.

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Résumé

Quiescent hematopoietic stem cells (HSCs) become activated and exit their bone marrow niches in response to infections or sterile inflammation to initiate extramedullary hematopoiesis at peripheral sites. While these processes have been described in acute infections, the impact of persistent viral infections on HSC activation and mobilization remains less clear. Our results demonstrate that an active persistent lymphocytic choriomeningitis virus (LCMV) clone 13 infection resulted in type I interferon-dependent stabilization of β-catenin in HSCs, promoting their activation, mobilization and functional exhaustion that was sustained in time and could be seen even after transfer to uninfected hosts. To further examine the functional role of β-catenin in HSC activation, we generated bone marrow chimeras to follow β-catenin-deficient (Ctnnb1−/−) and wild type HSC response to LCMV Cl13 in the same environment. Ctnnb1−/− HSCs and multipotent progenitor cells failed to expand in response to the infection, while still retaining their ability to reconstitute secondary hosts. Moreover, through the course of the infection, Ctnnb1−/− cells produced myeloid progeny at a similar level to the wild type. These findings lead us to propose that β-catenin is required for HSC activation by interferons in the early phase of the infection; however, it appears dispensable for LCMV-induced emergency myelopoiesis.

Type de document: Document issu d'une conférence ou d'un atelier
Informations complémentaires: Affiche scientifique Journal of Immunology (2021), 206 (suppl.1): 107.10
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Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 juin 2022 14:02
Dernière modification: 30 juin 2022 14:02
URI: https://espace.inrs.ca/id/eprint/12410

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