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J Immunol. 2009 Dec 15;183(12):7975-83. doi: 10.4049/jimmunol.0902718.

The Tpl2 mutation Sluggish impairs type I IFN production and increases susceptibility to group B streptococcal disease.

Author information

1
Department of Genetics, The Scripps Research Institute, La Jolla, CA 92037, USA.

Abstract

Sluggish was identified in a population of third generation mice descended from N-ethyl-N-nitrosourea-mutagenized sires. Macrophages from homozygotes exhibited impaired TNF-alpha production in response to all TLR ligands tested and displayed impaired type I IFN production in response to TLR7 and TLR9 stimulations. The phenotype was confined to a critical region on mouse chromosome 18 and then ascribed to a T to A transversion in the acceptor splice site of intron 4 at position 13346 of the Map3k8 gene, resulting in defective splicing. The Map3k8(Sluggish) mutation does not result in susceptibility to viral infections, but Sluggish mice displayed high susceptibility to group B streptococcus infection, with impaired TNF-alpha and type I IFN production in infected macrophages. Our data demonstrate that the encoded protein kinase Tpl2 plays an essential role in cell signaling in the immune response to certain pathogens.

PMID:
19923465
DOI:
10.4049/jimmunol.0902718
[Indexed for MEDLINE]
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