tetano
Editor, Senior Moderator
Nat Immunol. 2014 Nov 24. doi: 10.1038/ni.3046. [Epub ahead of print]
The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection.
Schliehe C1, Flynn EK2, Vilagos B1, Richson U1, Swaminathan S3, Bosnjak B4, Bauer L1, Kandasamy RK1, Griesshammer IM1, Kosack L1, Schmitz F3, Litvak V5, Sissons J3, Lercher A1, Bhattacharya A1, Khamina K1, Trivett AL2, Tessarollo L2, Mesteri I6, Hladik A7, Merkler D8, Kubicek S1, Knapp S7, Epstein MM4, Symer DE9, Aderem A3, Bergthaler A1.
Author information
Abstract
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.
PMID:
25419628
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25419628
The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection.
Schliehe C1, Flynn EK2, Vilagos B1, Richson U1, Swaminathan S3, Bosnjak B4, Bauer L1, Kandasamy RK1, Griesshammer IM1, Kosack L1, Schmitz F3, Litvak V5, Sissons J3, Lercher A1, Bhattacharya A1, Khamina K1, Trivett AL2, Tessarollo L2, Mesteri I6, Hladik A7, Merkler D8, Kubicek S1, Knapp S7, Epstein MM4, Symer DE9, Aderem A3, Bergthaler A1.
Author information
Abstract
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.
PMID:
25419628
[PubMed - as supplied by publisher]
http://www.ncbi.nlm.nih.gov/pubmed/25419628