Cargando…

The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection

Immune responses are tightly regulated to ensure efficient pathogen clearance while avoiding tissue damage. Here we report that SET domain bifurcated 2 (Setdb2) was the only protein lysine methyltransferase induced during influenza virus infection. Setdb2 expression depended on type-I interferon sig...

Descripción completa

Detalles Bibliográficos
Autores principales: Schliehe, Christopher, Flynn, Elizabeth K., Vilagos, Bojan, Richson, Udochuku, Swaminanthan, Savitha, Bosnjak, Berislav, Bauer, Lisa, Kandasamy, Richard K., Griesshammer, Isabel M., Kosack, Lindsay, Schmitz, Frank, Litvak, Vladimir, Sissons, James, Lercher, Alexander, Bhattacharya, Anannya, Khamina, Kseniya, Trivett, Anna L., Tessarollo, Lino, Mesteri, Ildiko, Hladik, Anastasiya, Merkler, Doron, Kubicek, Stefan, Knapp, Sylvia, Epstein, Michelle M., Symer, David E., Aderem, Alan, Bergthaler, Andreas
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320687/
https://www.ncbi.nlm.nih.gov/pubmed/25419628
http://dx.doi.org/10.1038/ni.3046
Descripción
Sumario:Immune responses are tightly regulated to ensure efficient pathogen clearance while avoiding tissue damage. Here we report that SET domain bifurcated 2 (Setdb2) was the only protein lysine methyltransferase induced during influenza virus infection. Setdb2 expression depended on type-I interferon signaling and it repressed the expression of the neutrophil attractant Cxcl1 and other NF-κB target genes. This coincided with Setdb2 occupancy at the Cxcl1 promoter, which in the absence of Setdb2 displayed reduced H3K9 tri-methylation. Setdb2 hypomorphic gene-trap mice exhibited increased neutrophil infiltration in sterile lung inflammation and were less sensitive to bacterial superinfection upon influenza virus infection. This suggests that a Setdb2-mediated regulatory crosstalk between the type-I interferon and NF-κB pathways represents an important mechanism for virus-induced susceptibility to bacterial superinfection.