HIF-1 stabilization in T cells hampers the control of Mycobacterium tuberculosis infection.

Autor: Liu R; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Muliadi V; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Mou W; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Capital Children's Hospital, Beijing, China., Li H; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Yuan J; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Holmberg J; Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden., Chambers BJ; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden., Ullah N; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Wurth J; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; University Children's Hospital Zurich, Zurich, Switzerland., Alzrigat M; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Schlisio S; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Carow B; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden.; Novovavax AB, Uppsala, Sweden., Larsson LG; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden., Rottenberg ME; Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden. martin.rottenberg@ki.se.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Sep 05; Vol. 13 (1), pp. 5093. Date of Electronic Publication: 2022 Sep 05.
DOI: 10.1038/s41467-022-32639-9
Abstrakt: The hypoxia-inducible factors (HIFs) regulate the main transcriptional pathway of response to hypoxia in T cells and are negatively regulated by von Hippel-Lindau factor (VHL). But the role of HIFs in the regulation of CD4 T cell responses during infection with M. tuberculosis isn't well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection with M. tuberculosis, which is associated with a low accumulation of mycobacteria-specific T cells in the lungs that display reduced proliferation, altered differentiation and enhanced expression of inhibitory receptors. In contrast, HIF-1 deficiency in T cells is redundant for M. tuberculosis control. Vhl cKO mice also show reduced responses to vaccination. Further, VHL promotes proper MYC-activation, cell-growth responses, DNA synthesis, proliferation and survival of CD4 T cells after TCR activation. The VHL-deficient T cell responses are rescued by the loss of HIF-1α, indicating that the increased susceptibility to M. tuberculosis infection and the impaired responses of Vhl-deficient T cells are HIF-1-dependent.
(© 2022. The Author(s).)
Databáze: MEDLINE
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