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Resch, Ulrike
Publications (2 of 2) Show all publications
Erttmann, S. F., Härtlova, A., Sloniecka, M., Raffi, F. A. M., Hosseinzadeh, A., Edgren, T., . . . Gekara, N. O. (2016). Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity. Immunity, 45(1), 106-118
Open this publication in new window or tab >>Loss of the DNA Damage Repair Kinase ATM Impairs Inflammasome-Dependent Anti-Bacterial Innate Immunity
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2016 (English)In: Immunity, ISSN 1074-7613, E-ISSN 1097-4180, Vol. 45, no 1, p. 106-118Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Immunology in the medical area
Identifiers
urn:nbn:se:umu:diva-125590 (URN)10.1016/j.immuni.2016.06.018 (DOI)000380749000014 ()27421701 (PubMedID)
Available from: 2016-09-23 Created: 2016-09-13 Last updated: 2018-06-07Bibliographically approved
Härtlova, A., Link, M., Balounova, J., Benesova, M., Resch, U., Straskova, A., . . . Stulik, J. (2014). Quantitative proteomics analysis of macrophage-derived lipid rafts reveals induction of autophagy pathway at the early time of Francisella tularensis LVS infection. Journal of Proteome Research, 13(2), 796-804
Open this publication in new window or tab >>Quantitative proteomics analysis of macrophage-derived lipid rafts reveals induction of autophagy pathway at the early time of Francisella tularensis LVS infection
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2014 (English)In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 13, no 2, p. 796-804Article in journal (Refereed) Published
Abstract [en]

Francisella tularensis is a highly infectious intracellular pathogen that has evolved an efficient strategy to subvert host defense response to survive inside the host. The molecular mechanisms regulating these host-pathogen interactions and especially those that are initiated at the time of the bacterial entry via its attachment to the host plasma membrane likely predetermine the intracellular fate of pathogen. Here, we provide the evidence that infection of macrophages with F. tularensis leads to changes in protein composition of macrophage-derived lipid rafts, isolated as detergent-resistant membranes (DRMs). Using SILAC-based quantitative proteomic approach, we observed the accumulation of autophagic adaptor protein p62 at the early, stages of microbe-host cell interaction. We confirmed the colocalization of the p62 with ubiquitinated and LC3-decorated intracellular F. tularensis microbes with its maximum at 1 h postinfection. Furthermore, the infection of p62-knockdown host cells led to the transient increase in the intracellular number of microbes up to 4 h after in vitro infection. Together, these data suggest that the activation of the autophagy pathway in F. tularensis infected macrophages, which impacts the early phase of microbial proliferation, is subsequently circumvented by ongoing infection.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-87175 (URN)10.1021/pr4008656 (DOI)000331164100040 ()
Available from: 2014-03-31 Created: 2014-03-24 Last updated: 2018-06-08Bibliographically approved
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