1. The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
- Author
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Fernandes-Alnemri, Teresa, Yu, Je-Wook, Juliana, Christine, Solorzano, Leobaldo, Kang, Seokwon, Wu, Jianghong, Datta, Pinaki, McCormick, Margaret, Huang, Lan, McDermott, Erin, Eisenlohr, Laurence, Landel, Carlisle P, and Alnemri, Emad S
- Subjects
Immunization ,Prevention ,Vaccine Related ,Biodefense ,Emerging Infectious Diseases ,Infectious Diseases ,Animals ,Calcium Signaling ,Caspase 1 ,Cells ,Cultured ,DNA-Binding Proteins ,Francisella tularensis ,Humans ,Immunity ,Innate ,Interferon Regulatory Factor-3 ,Interferon Type I ,Interleukin-1beta ,L-Lactate Dehydrogenase ,Macrophages ,Mice ,Mice ,Knockout ,Multiprotein Complexes ,Nuclear Proteins ,Protein Multimerization ,Tularemia ,Immunology - Abstract
Francisella tularensis, the causative agent of tularemia, infects host macrophages, which triggers production of the proinflammatory cytokines interleukin 1beta (IL-1beta) 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-1beta 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.
- Published
- 2010