Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity.

Autor:	Erttmann SF; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Härtlova A; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Sloniecka M; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Raffi FA; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Hosseinzadeh A; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden; Department of Clinical Microbiology, Umeå University, Umeå 901 87, Sweden., Edgren T; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Rofougaran R; Department of Biochemistry, Institute of Biochemistry and Biophysics, Tehran University, Tehran, Iran., Resch U; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Fällman M; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden., Ek T; Department of Paediatrics, Hospital of Halland, 30185 Halmstad, Sweden., Gekara NO; Laboratory for Molecular Infection Medicine Sweden (MIMS), Umeå University, Umeå 901 87, Sweden; Department of Molecular Biology, Umeå University, Umeå 901 87, Sweden; Umeå Centre for Microbial Research (UCMR), Umeå University, Umeå 901 87, Sweden. Electronic address: nelson.gekara@mims.umu.se.
Jazyk:	angličtina
Zdroj:	Immunity [Immunity] 2016 Jul 19; Vol. 45 (1), pp. 106-18. Date of Electronic Publication: 2016 Jul 12.
DOI:	10.1016/j.immuni.2016.06.018
Abstrakt:	The ATM kinase is a central component of the DNA damage repair machinery and redox balance. ATM dysfunction results in the multisystem disease ataxia-telangiectasia (AT). A major cause of mortality in AT is respiratory bacterial infections. Whether ATM deficiency causes innate immune defects that might contribute to bacterial infections is not known. Here we have shown that loss of ATM impairs inflammasome-dependent anti-bacterial innate immunity. Cells from AT patients or Atm(-/-) mice exhibited diminished interleukin-1β (IL-1β) production in response to bacteria. In vivo, Atm(-/-) mice were more susceptible to pulmonary S. pneumoniae infection in a manner consistent with inflammasome defects. Our data indicate that such defects were due to oxidative inhibition of inflammasome complex assembly. This study reveals an unanticipated function of reactive oxygen species (ROS) in negative regulation of inflammasomes and proposes a theory for the notable susceptibility of AT patients to pulmonary bacterial infection. (Copyright © 2016 Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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