| First Author | Banks DA | Year | 2019 |
| Journal | J Immunol | Volume | 202 |
| Issue | 8 | Pages | 2348-2359 |
| PubMed ID | 30833347 | Mgi Jnum | J:274565 |
| Mgi Id | MGI:6287917 | Doi | 10.4049/jimmunol.1801303 |
| Citation | Banks DA, et al. (2019) Mycobacterium tuberculosis Inhibits Autocrine Type I IFN Signaling to Increase Intracellular Survival. J Immunol 202(8):2348-2359 |
| abstractText | The type I IFNs (IFN-alpha and -beta) are important for host defense against viral infections. In contrast, their role in defense against nonviral pathogens is more ambiguous. In this article, we report that IFN-beta signaling in murine bone marrow-derived macrophages has a cell-intrinsic protective capacity against Mycobacterium tuberculosis via the increased production of NO. The antimycobacterial effects of type I IFNs were mediated by direct signaling through the IFN-alpha/beta-receptor (IFNAR), as Ab-mediated blocking of IFNAR1 prevented the production of NO. Furthermore, M. tuberculosis is able to inhibit IFNAR-mediated cell signaling and the subsequent transcription of 309 IFN-beta-stimulated genes in a dose-dependent way. The molecular mechanism of inhibition by M. tuberculosis involves reduced phosphorylation of the IFNAR-associated protein kinases JAK1 and TYK2, leading to reduced phosphorylation of the downstream targets STAT1 and STAT2. Transwell experiments demonstrated that the M. tuberculosis-mediated inhibition of type I IFN signaling was restricted to infected cells. Overall, our study supports the novel concept that M. tuberculosis evolved to inhibit autocrine type I IFN signaling to evade host defense mechanisms. |
