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Publication : A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection.

First Author  Ranjbar S Year  2015
Journal  Cell Rep Volume  13
Issue  5 Pages  874-83
PubMed ID  26565900 Mgi Jnum  J:228955
Mgi Id  MGI:5749894 Doi  10.1016/j.celrep.2015.09.048
Citation  Ranjbar S, et al. (2015) A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection. Cell Rep 13(5):874-83
abstractText  The interferon (IFN)-induced transmembrane (IFITM) proteins are critical mediators of the host antiviral response. Here, we expand the role of IFITM proteins to host defense against intracellular bacterial infection by demonstrating that they restrict Mycobacterium tuberculosis (MTb) intracellular growth. Simultaneous knockdown of IFITM1, IFITM2, and IFITM3 by RNAi significantly enhances MTb growth in human monocytic and alveolar/epithelial cells, whereas individual overexpression of each IFITM impairs MTb growth in these cell types. Furthermore, MTb infection, Toll-like receptor 2 and 4 ligands, and several proinflammatory cytokines induce IFITM1-3 gene expression in human myeloid cells. We find that IFITM3 co-localizes with early and, in particular, late MTb phagosomes, and overexpression of IFITM3 enhances endosomal acidification in MTb-infected monocytic cells. These findings provide evidence that the antiviral IFITMs participate in the restriction of mycobacterial growth, and they implicate IFITM-mediated endosomal maturation in its antimycobacterial activity.
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