PT  - JOURNAL ARTICLE
AU  - Yong Cheng
AU  - Jeffery S. Schorey
TI  - Extracellular Vesicles promote host immunity during an <em>M. tuberculosis</em> infection through RNA Sensing
AID  - 10.1101/346254
DP  - 2018 Jan 01
TA  - bioRxiv
PG  - 346254
4099  - http://biorxiv.org/content/early/2018/06/15/346254.short
4100  - http://biorxiv.org/content/early/2018/06/15/346254.full
AB  - Extracellular vesicles (EVs) have been shown to carry microbial components and function in the host defense against infections. In this study, we demonstrate that Mycobacterium tuberculosis (M.tb) RNA is delivered into macrophage-derived EVs through an M.tb SecA2-dependent pathway, and that EVs released from M.tb-infected macrophages stimulate a host RIG-I/MAVS/TBK1/IRF3 RNA sensing pathway, leading to type I interferon production in recipient cells. These EVs also promote, in a RIG-I/MAVS-dependent manner, the maturation of M.tb-containing phagosomes through a noncanonical LC3 modification, leading to increased bacterial killing. Moreover, treatment of M.tb-infected macrophages or mice with a combination of moxifloxacin and EVs, isolated from M.tb-infected macrophages, significantly lowered bacterial burden relative to either treatment alone. We propose that EVs, which are preferentially removed by macrophages in vivo, may be developed in combination with effective antibiotics as a novel approach to treat drug-resistant TB.