Mycobacterium tuberculosis inhibits autocrine type I interferon signaling to increase intracellular survival
Mycobacterium tuberculosis inhibits autocrine type I interferon signaling to increase intracellular survival
Summary The type I interferons (IFN-α and -β) are important for host defense against viral infections. In contrast, their role in defense against non-viral pathogens is more ambiguous. Here we report that IFN-β-signaling in macrophages has protective capacity against Mycobacterium tuberculosis (Mtb) via the increased production of nitric oxide. Furthermore, Mtb is able to inhibit IFN-α/β-receptor-mediated cell signaling and the transcription of 309 IFN-β stimulated genes which includes genes associated with innate host cell defense. The molecular mechanism of inhibition by Mtb involves reduced phosphorylation of the IFNAR-associated protein kinases JAK1 and TYK2 leading to reduced phosphorylation of the downstream targets STAT1 and STAT2. Overall, our study supports the novel concept that Mtb evolved to inhibit autocrine type I IFN signaling in order to evade host defense mechanisms.
Banks Dallas A.、Keith Hughitt V.、Shah Swati、Vogel Stefanie N.、El-Sayed Najib M.、Briken Volker、Ahlbrand Sarah E.
Department of Cell Biology and Molecular Genetics, University of MarylandDepartment of Cell Biology and Molecular Genetics, University of Maryland||Center for Bioinformatics and Computational Biology, University of MarylandDepartment of Cell Biology and Molecular Genetics, University of MarylandDepartment of Microbiology and Immunology, University of Maryland School of MedicineDepartment of Cell Biology and Molecular Genetics, University of Maryland||Center for Bioinformatics and Computational Biology, University of MarylandDepartment of Cell Biology and Molecular Genetics, University of MarylandDepartment of Cell Biology and Molecular Genetics, University of Maryland
基础医学微生物学分子生物学
Banks Dallas A.,Keith Hughitt V.,Shah Swati,Vogel Stefanie N.,El-Sayed Najib M.,Briken Volker,Ahlbrand Sarah E..Mycobacterium tuberculosis inhibits autocrine type I interferon signaling to increase intracellular survival[EB/OL].(2025-03-28)[2025-05-13].https://www.biorxiv.org/content/10.1101/425116.点此复制
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