Abstract
AbstractThe 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 withM. tuberculosisisn’t well understood. Here we show that mice lacking VHL in T cells (Vhl cKO) are highly susceptible to infection withM. 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 forM. tuberculosiscontrol.Vhl cKOmice 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 toM. tuberculosisinfection and the impaired responses ofVhl-deficient T cells are HIF-1-dependent.
Funder
Vetenskapsrådet
Swedish Foundation for International Cooperation in Research and Higher Education
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Cited by
16 articles.
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