Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis.

Détails

ID Serval
serval:BIB_FA9D8A005A28
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Absent in melanoma 2 is required for innate immune recognition of Francisella tularensis.
Périodique
Proceedings of the National Academy of Sciences of the United States of America
Auteur(s)
Jones J.W., Kayagaki N., Broz P., Henry T., Newton K., O'Rourke K., Chan S., Dong J., Qu Y., Roose-Girma M., Dixit V.M., Monack D.M.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Statut éditorial
Publié
Date de publication
2010
Peer-reviewed
Oui
Volume
107
Numéro
21
Pages
9771-9776
Langue
anglais
Résumé
Macrophages respond to cytosolic nucleic acids by activating cysteine protease caspase-1 within a complex called the inflammasome. Subsequent cleavage and secretion of proinflammatory cytokines IL-1beta and IL-18 are critical for innate immunity. Here, we show that macrophages from mice lacking absent in melanoma 2 (AIM2) cannot sense cytosolic double-stranded DNA and fail to trigger inflammasome assembly. Caspase-1 activation in response to intracellular pathogen Francisella tularensis also required AIM2. Immunofluorescence microscopy of macrophages infected with F. tularensis revealed striking colocalization of bacterial DNA with endogenous AIM2 and inflammasome adaptor ASC. By contrast, type I IFN (IFN-alpha and -beta) secretion in response to F. tularensis did not require AIM2. IFN-I did, however, boost AIM2-dependent caspase-1 activation by increasing AIM2 protein levels. Thus, inflammasome activation was reduced in infected macrophages lacking either the IFN-I receptor or stimulator of interferon genes (STING). Finally, AIM2-deficient mice displayed increased susceptibility to F. tularensis infection compared with wild-type mice. Their increased bacterial burden in vivo confirmed that AIM2 is essential for an effective innate immune response.

Mots-clé
Animals, Caspase 1/metabolism, Cells, Cultured, Cytosol/immunology, DNA/genetics, DNA/immunology, DNA-Binding Proteins, Enzyme Activation, Francisella tularensis/immunology, Immunity, Innate, Interferon-alpha/immunology, Interferon-beta/immunology, Mice, Mice, Inbred C57BL, Mice, Knockout, Nuclear Proteins/deficiency, Nuclear Proteins/immunology, Receptor, Interferon alpha-beta/immunology, Tularemia/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/10/2017 11:05
Dernière modification de la notice
20/08/2019 17:26
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