The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
Copyright policy )The AIM2 inflammasome is critical for innate immunity to Francisella tularensis
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.
- University of California, San Francisco United States
- Myongji University Korea (Republic of)
- THOMAS JEFFERSON UNIVERSITY
- Thomas Jefferson University United States
Cells, Knockout, Immunology, Interleukin-1beta, Article, Vaccine Related, Mice, Biodefense, Innate, Animals, Humans, Calcium Signaling, Francisella tularensis, Tularemia, Cells, Cultured, Mice, Knockout, Cultured, L-Lactate Dehydrogenase, Prevention, Macrophages, Caspase 1, Immunity, Nuclear Proteins, Immunity, Innate, DNA-Binding Proteins, Emerging Infectious Diseases, Infectious Diseases, Multiprotein Complexes, Interferon Type I, Immunization, Interferon Regulatory Factor-3, Protein Multimerization
Cells, Knockout, Immunology, Interleukin-1beta, Article, Vaccine Related, Mice, Biodefense, Innate, Animals, Humans, Calcium Signaling, Francisella tularensis, Tularemia, Cells, Cultured, Mice, Knockout, Cultured, L-Lactate Dehydrogenase, Prevention, Macrophages, Caspase 1, Immunity, Nuclear Proteins, Immunity, Innate, DNA-Binding Proteins, Emerging Infectious Diseases, Infectious Diseases, Multiprotein Complexes, Interferon Type I, Immunization, Interferon Regulatory Factor-3, Protein Multimerization
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