A Role for IFITM Proteins in Restriction of Mycobacterium tuberculosis Infection

Ranjbar, Shahin; Haridas, Viraga; Jasenosky, Luke D.; Falvo, James V.; Goldfeld, Anne E.

Arrest of phagosome maturation is a hallmark of virulent MTb infection (Armstrong and Hart, 1971) . A mechanism of MTb-mediated phagosome arrest is the exclusion of the host v-ATPase from the phagosomal membrane (Sturgill-Koszycki et al., 1994; Wong et al., 2011) . Notably, IFITM3 overexpression leads to an increase in the size and number of acidic compartments in murine and human cells (Feeley et al., 2011; Mudhasani et al., 2013; Wee et al., 2012) , and IFITM3 interacts with v-ATPase and potentially stabilizes its association with endosomal membranes (Wee et al., 2012) . Our findings that IFITM3 co-localizes with the MTb phagosome and that increased IFITM3-mediated intracellular acidity is maintained even in the presence of MTb infection suggest that IFITM3 (and potentially IFITM1/2) impedes productive MTb infection in a manner similar to its antiviral role. Because several other pathogenic intracellular bacteria, including Salmonella enterica and Yersinia pestis, also depend on phagosomal maturation arrest for survival and growth (Smith and May, 2013) , it is possible that the IFITMs may contribute to host control of a diverse range of bacterial pathogens.