期刊
MICROBES AND INFECTION
卷 21, 期 2, 页码 85-93出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.micinf.2018.09.001
关键词
Innate immunity; Inflammasome; AIM2; Dendritic cells; Brucella abortus; DNA sensing
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPQ) [302660/2015-1, 402527/2013--5]
- Fundacao de Amparoa Pesquisa do estado de Minas Gerais (FAPEMIG) grant APQ [-00837/15, 01945/17]
- Fundacao de Amparoa Pesquisa do estado de Minas Gerais (FAPEMIG) grant Rede Mineira de Imunobiologicos [RED-140-16]
- National Institute of Health [R01 AI116453]
Absent in melanoma 2 (AIM2) is a sensor of cytosolic dsDNA and is responsible for the activation of inflammatory and host immune responses to DNA viruses and intracellular bacteria. AIM2 is a member of the hematopoietic interferon-inducible nuclear proteins with a 200 amino-acid repeat (HIN200) family, containing a pyrin domain (PYD) at the N-terminus. Several studies have demonstrated that AIM2 is responsible for host defense against intracellular bacteria such as Francisella tularensis, Listeria monocytogenes and Mycobacerium tuberculosis. However, the role of AIM2 in host defenses against Brucella is poorly understood. In this study, we have shown that AIM2 senses Brucella DNA in dendritic cells to induce pyroptosis and regulates type I IFN. Confocal microscopy of infected cells revealed co-localization between Brucella DNA and endogenous AIM2. Dendritic cells from AIM2 KO mice infected with B. abortus showed impaired secretion of IL-1 beta as well as compromised caspase-1 cleavage. AIM2 KO mice displayed increased susceptibility to B. abortus infection in comparison to wild-type mice, and this susceptibility was associated with defective IL-1 beta production together with reduced IFN-gamma responses. In summary, the increased bacterial burden observed in vivo in AIM2 KO animals confirmed that AIM2 is essential for an effective innate immune response against Brucella infection. (C) 2018 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据