BACKGROUND: Mycobacterium bovis, the causative agent of bovine tuberculosis, infects host macrophages and triggers production of the proinflammatory cytokine interleukin 1β (IL-1β). The mechanism by which macrophages become activated and secrete IL-1β in tuberculosis has not yet been elucidated. METHODS: In this study, we investigated the role of the absence in melanoma 2 (AIM2) inflammasome in IL-1β release from macrophages infected with pathogenic M. bovis strain. RESULTS: We found that the AIM2 inflammasome activation is involved in the production of IL-1β in primary and immortalized mouse macrophage upon M. bovis infection; that the activation process requires cytoplasmic potassium efflux, mycobacterial internalization, but not reactive oxygen species (ROS) or IFN-β release; that the AIM2 inflammasome contributes to the synthesis of proinflammatory and chemotatic factors in M. bovis-infected macrophages; and that the activation of the AIM2 inflammasome is due, at least in part, to mycobacterial translocation into the cytosol. CONCLUSIONS: We conclude that the AIM2 inflammasome is involved in macrophage activation during infection with virulent M. bovis strain. To our knowledge, this is the first evidences for the involvement of the AIM2 inflammasome in M. bovis infection.
BACKGROUND:Mycobacterium bovis, the causative agent of bovinetuberculosis, infects host macrophages and triggers production of the proinflammatory cytokine interleukin 1β (IL-1β). The mechanism by which macrophages become activated and secrete IL-1β in tuberculosis has not yet been elucidated. METHODS: In this study, we investigated the role of the absence in melanoma 2 (AIM2) inflammasome in IL-1β release from macrophages infected with pathogenic M. bovis strain. RESULTS: We found that the AIM2 inflammasome activation is involved in the production of IL-1β in primary and immortalized mouse macrophage upon M. bovis infection; that the activation process requires cytoplasmic potassium efflux, mycobacterial internalization, but not reactive oxygen species (ROS) or IFN-β release; that the AIM2 inflammasome contributes to the synthesis of proinflammatory and chemotatic factors in M. bovis-infected macrophages; and that the activation of the AIM2 inflammasome is due, at least in part, to mycobacterial translocation into the cytosol. CONCLUSIONS: We conclude that the AIM2 inflammasome is involved in macrophage activation during infection with virulent M. bovis strain. To our knowledge, this is the first evidences for the involvement of the AIM2 inflammasome in M. bovis infection.
Entities:
Keywords:
AIM2; IL-1β; M. bovis; inflammasome; macrophage
Authors: Takanori Komada; Hyunjae Chung; Arthur Lau; Jaye M Platnich; Paul L Beck; Hallgrimur Benediktsson; Henry J Duff; Craig N Jenne; Daniel A Muruve Journal: J Am Soc Nephrol Date: 2018-02-09 Impact factor: 10.121