Mycobacterium tuberculosis induces the miR-33 locus to reprogram autophagy and host lipid metabolism.
Nat Immunol
; 17(6): 677-86, 2016 06.
Article
en En
| MEDLINE
| ID: mdl-27089382
ABSTRACT
Mycobacterium tuberculosis (Mtb) survives in macrophages by evading delivery to the lysosome and promoting the accumulation of lipid bodies, which serve as a bacterial source of nutrients. We found that by inducing the microRNA (miRNA) miR-33 and its passenger strand miR-33*, Mtb inhibited integrated pathways involved in autophagy, lysosomal function and fatty acid oxidation to support bacterial replication. Silencing of miR-33 and miR-33* by genetic or pharmacological means promoted autophagy flux through derepression of key autophagy effectors (such as ATG5, ATG12, LC3B and LAMP1) and AMPK-dependent activation of the transcription factors FOXO3 and TFEB, which enhanced lipid catabolism and Mtb xenophagy. These data define a mammalian miRNA circuit used by Mtb to coordinately inhibit autophagy and reprogram host lipid metabolism to enable intracellular survival and persistence in the host.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Autofagia
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Tuberculosis
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MicroARNs
/
Metabolismo de los Lípidos
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Lisosomas
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Macrófagos
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Mycobacterium tuberculosis
Límite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Nat Immunol
Asunto de la revista:
ALERGIA E IMUNOLOGIA
Año:
2016
Tipo del documento:
Article
País de afiliación:
Estados Unidos