State Key Laboratories for Agrobiotechnology, Key Lab of Animal Epidemiology and Zoonosis, Ministry of Agriculture, National Animal Transmissible Spongiform Encephalopathy Laboratory, College of Veterinary Medicine, China Agricultural University, Beijing.
J Infect Dis. 2013 Dec 1;208(11):1849-58. doi: 10.1093/infdis/jit347. Epub 2013 Jul 30.
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.
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.
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.
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.
牛分枝杆菌是牛结核病的病原体，它感染宿主巨噬细胞并引发促炎细胞因子白细胞介素 1β（IL-1β）的产生。巨噬细胞在结核病中被激活并分泌 IL-1β的机制尚未阐明。
在本研究中，我们研究了黑色素瘤缺失 2（AIM2）炎症小体在感染致病性牛分枝杆菌菌株的巨噬细胞中释放 IL-1β中的作用。
我们发现，AIM2 炎症小体的激活参与了原发性和永生化的小鼠巨噬细胞在牛分枝杆菌感染后的 IL-1β 的产生；该激活过程需要细胞质钾离子外流、分枝杆菌内化，但不需要活性氧（ROS）或 IFN-β 的释放；AIM2 炎症小体有助于牛分枝杆菌感染的巨噬细胞中促炎和趋化因子的合成；并且 AIM2 炎症小体的激活至少部分是由于分枝杆菌易位到细胞质中。
我们得出结论，AIM2 炎症小体参与了强毒力牛分枝杆菌菌株感染期间的巨噬细胞激活。据我们所知，这是 AIM2 炎症小体参与牛分枝杆菌感染的首次证据。
