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Extracellular Vesicles promote host immunity during an M. tuberculosis infection through RNA Sensing

journal contribution
posted on 2018-10-29, 00:00 authored by Jeff Schorey, Yong Cheng
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.

History

Date Modified

2019-07-30

Language

  • English

Publisher

Cold Sring Harbor Laboratory

Additional Groups

  • Eck Institute for Global Health
  • Integrated Imaging Facility
  • Biological Sciences
  • Center for Rare and Neglected Diseases

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    Biological Sciences

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