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  • Erttmann, Saskia F.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR) (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • Elsevier BV,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-125590
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-125590URI
  • https://doi.org/10.1016/j.immuni.2016.06.018DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Härtlova, AnettaUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)anha0317 (author)
  • Sloniecka, MartaUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)masl0011 (author)
  • Raffi, Faizal A. M.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)faal0008 (author)
  • Hosseinzadeh, AvaUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Umeå Centre for Microbial Research (UCMR),Institutionen för klinisk mikrobiologi(Swepub:umu)avho0003 (author)
  • Edgren, TomasUmeå universitet,Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)toed0004 (author)
  • Rofougaran, Reza (author)
  • Resch, UlrikeUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)ulre0011 (author)
  • Fällman, MariaUmeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR) (author)
  • Ek, Torben (author)
  • Gekara, Nelson O.Umeå universitet,Molekylär Infektionsmedicin, Sverige (MIMS),Institutionen för molekylärbiologi (Medicinska fakulteten),Umeå Centre for Microbial Research (UCMR)(Swepub:umu)fepe0003 (author)
  • Umeå universitetMolekylär Infektionsmedicin, Sverige (MIMS) (creator_code:org_t)

Related titles

  • In:Immunity: Elsevier BV45:1, s. 106-1181074-76131097-4180

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