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 PMID:25419628  

The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection.

Christopher Schliehe | Elizabeth K Flynn | Bojan Vilagos | Udochuku Richson | Savitha Swaminanthan | Berislav Bosnjak | Lisa Bauer | Richard K Kandasamy | Isabel M Griesshammer | Lindsay Kosack | Frank Schmitz | Vladimir Litvak | James Sissons | Alexander Lercher | Anannya Bhattacharya | Kseniya Khamina | Anna L Trivett | Lino Tessarollo | Ildiko Mesteri | Anastasiya Hladik | Doron Merkler | Stefan Kubicek | Sylvia Knapp | Michelle M Epstein | David E Symer | Alan Aderem | Andreas Bergthaler
Nature immunology | 2015

Immune responses are tightly regulated to ensure efficient pathogen clearance while avoiding tissue damage. Here we report that Setdb2 was the only protein lysine methyltransferase induced during infection with influenza virus. Setdb2 expression depended on signaling via type I interferons, and Setdb2 repressed expression of the gene encoding the neutrophil attractant CXCL1 and other genes that are targets of the transcription factor NF-κB. This coincided with occupancy by Setdb2 at the Cxcl1 promoter, which in the absence of Setdb2 displayed diminished trimethylation of histone H3 Lys9 (H3K9me3). Mice with a hypomorphic gene-trap construct of Setdb2 exhibited increased infiltration of neutrophils during sterile lung inflammation and were less sensitive to bacterial superinfection after infection with influenza virus. This suggested that a Setdb2-mediated regulatory crosstalk between the type I interferons and NF-κB pathways represents an important mechanism for virus-induced susceptibility to bacterial superinfection.

Pubmed ID: 25419628

Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: R01 AI032972
  • Agency: NIAID NIH HHS, United States
    Id: R01AI032972
  • Agency: NIAID NIH HHS, United States
    Id: U19 AI100627
  • Agency: NIAID NIH HHS, United States
    Id: R01AI025032
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI025032
  • Agency: NIAID NIH HHS, United States
    Id: U19AI100627
  • Agency: Austrian Science Fund FWF, Austria
    Id: P 25360

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