The methyltransferase Setdb2 mediates virus-induced susceptibility to bacterial superinfection.
Nat Immunol
; 16(1): 67-74, 2015 Jan.
Article
em En
| MEDLINE
| ID: mdl-25419628
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Orthomyxoviridae
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Pneumonia
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Superinfecção
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NF-kappa B
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Histona-Lisina N-Metiltransferase
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Infecções por Orthomyxoviridae
Limite:
Animals
Idioma:
En
Revista:
Nat Immunol
Ano de publicação:
2015
Tipo de documento:
Article