Premium
Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing
Author(s) -
Cheng Yong,
Schorey Jeffery S
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846613
Subject(s) - library science , computer science
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 / TBK 1/ IRF 3 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 LC 3 pathway, 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 hypothesize that EVs, which are preferentially removed by macrophages in vivo , can be combined with effective antibiotics as a novel approach to treat drug‐resistant TB .