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The AIM2 inflammasome is critical for innate immunity to Francisella tularensis

Authors
 Teresa Fernandes-Alnemri  ;  Je-Wook Yu  ;  Christine Juliana  ;  Leobaldo Solorzano  ;  Seokwon Kang  ;  Jianghong Wu  ;  Pinaki Datta  ;  Margaret McCormick  ;  Lan Huang  ;  Erin McDermott  ;  Laurence Eisenlohr  ;  Carlisle P. Landel  ;  Emad S. Alnemri 
Citation
 NATURE IMMUNOLOGY, Vol.11(5) : 385-393, 2010 
Journal Title
NATURE IMMUNOLOGY
ISSN
 1529-2908 
Issue Date
2010
MeSH
Animals ; Calcium Signaling/immunology ; Caspase 1/genetics ; Caspase 1/immunology ; Caspase 1/metabolism ; Cells, Cultured ; DNA-Binding Proteins ; Francisella tularensis/immunology* ; Francisella tularensis/pathogenicity ; Humans ; Immunity, Innate* ; Interferon Regulatory Factor-3/genetics ; Interferon Regulatory Factor-3/immunology ; Interferon Regulatory Factor-3/metabolism ; Interferon Type I/immunology ; Interleukin-1beta/biosynthesis ; Interleukin-1beta/genetics ; Interleukin-1beta/immunology ; L-Lactate Dehydrogenase/genetics ; L-Lactate Dehydrogenase/immunology ; L-Lactate Dehydrogenase/metabolism ; Macrophages/immunology ; Macrophages/metabolism* ; Macrophages/pathology ; Mice ; Mice, Knockout ; Multiprotein Complexes/genetics ; Multiprotein Complexes/immunology ; Multiprotein Complexes/metabolism* ; Nuclear Proteins/genetics ; Nuclear Proteins/immunology* ; Nuclear Proteins/metabolism* ; Protein Multimerization ; Tularemia/genetics ; Tularemia/immunology* ; Tularemia/metabolism
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
Files in This Item:
T201005886.pdf Download
DOI
10.1038/ni.1859.
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Microbiology (미생물학교실) > 1. Journal Papers
Yonsei Authors
Yu, Je Wook(유제욱) ORCID logo https://orcid.org/0000-0001-5943-4071
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/103242
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