Extracellular vesicles deliver Mycobacterium RNA to promote host immunity and bacterial killing.
EMBO Rep
; 20(3)2019 03.
Article
em En
| MEDLINE
| ID: mdl-30683680
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
RNA Bacteriano
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Viabilidade Microbiana
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Interações Hospedeiro-Patógeno
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Vesículas Extracelulares
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Imunidade
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Mycobacterium tuberculosis
Limite:
Animals
Idioma:
En
Revista:
EMBO Rep
Ano de publicação:
2019
Tipo de documento:
Article