The AIM2 inflammasome is critical for innate immunity to Francisella tularensis

被引：574

作者：

Fernandes-Alnemri, Teresa ^{[1
,3
]}

Yu, Je-Wook ^{[1
,3
]}

Juliana, Christine ^{[1
,3
]}

Solorzano, Leobaldo ^{[1
,3
]}

Kang, Seokwon ^{[1
,3
]}

Wu, Jianghong ^{[1
,3
]}

Datta, Pinaki ^{[1
,3
]}

McCormick, Margaret ^{[1
,3
]}

Huang, Lan ^{[2
,3
]}

McDermott, Erin ^{[2
,3
]}

Eisenlohr, Laurence ^{[2
,3
]}

Landel, Carlisle P. ^{[2
,3
]}

Alnemri, Emad S. ^{[1
,3
]}

机构：

[1] Thomas Jefferson Univ, Dept Biochem & Mol Biol, Philadelphia, PA 19107 USA

[2] Thomas Jefferson Univ, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA

[3] Thomas Jefferson Univ, Kimmel Canc Ctr, Philadelphia, PA 19107 USA

来源：

NATURE IMMUNOLOGY | 2010年 / 11卷 / 05期

基金：

美国国家卫生研究院;

关键词：

NF-KAPPA-B; PATHOGEN RECOGNITION; NALP3; INFLAMMASOME; PHAGOSOMAL ESCAPE; ASC PYROPTOSOME; CYTOPLASMIC DNA; CELL-DEATH; ACTIVATION; CASPASE-1; PYRIN;

D O I：

10.1038/ni.1859

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1 beta (IL-1 beta) and IL-18. We elucidate here how host macrophages recognize F. tularensis and elicit this proinflammatory response. Using mice deficient in the DNA-sensing inflammasome component AIM2, we demonstrate here that AIM2 is required for sensing F. tularensis. AIM2-deficient mice were extremely susceptible to F. tularensis infection, with greater mortality and bacterial burden than that of wild-type mice. Caspase-1 activation, IL-1 beta secretion and cell death were absent in Aim2(-/-) macrophages in response to F. tularensis infection or the presence of cytoplasmic DNA. Our study identifies AIM2 as a crucial sensor of F. tularensis infection and provides genetic proof of its critical role in host innate immunity to intracellular pathogens.

引用

页码：385 / 394

页数：10

共 45 条

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