Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing.

Abstract:

: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 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.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Cheng Y,Schorey JS

doi

10.15252/embr.201846613

subject

Has Abstract

pub_date

2019-03-01 00:00:00

issue

3

eissn

1469-221X

issn

1469-3178

pii

embr.201846613

journal_volume

20

pub_type

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