Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity
2016 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 45, no 1, 106-118 p.Article in journal (Refereed) Published
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-1 beta (IL-1 beta) 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.
Place, publisher, year, edition, pages
2016. Vol. 45, no 1, 106-118 p.
Immunology in the medical area
IdentifiersURN: urn:nbn:se:umu:diva-125590DOI: 10.1016/j.immuni.2016.06.018ISI: 000380749000014PubMedID: 27421701OAI: oai:DiVA.org:umu-125590DiVA: diva2:973951