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

The Journal of Immunology : Official Journal of the American Association of Immunologists
Nengming XiaoBruce Beutler

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.

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Citations

Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Owen M SiggsBruce Beutler
Jun 29, 2011·Proceedings of the National Academy of Sciences of the United States of America·Daniel E ZakAlan Aderem
May 9, 2013·Clinical & Developmental Immunology·Ashley M Sherrid, Tobias R Kollmann
Oct 4, 2017·The Journal of Experimental Medicine·Lei SunBruce Beutler
Nov 6, 2013·Journal of Neurochemistry·Joshua HirschhornNarayan R Bhat
Jul 12, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Finlay W McNabAnne O'Garra
Sep 26, 2012·The Journal of Immunology : Official Journal of the American Association of Immunologists·Amber KaplanDavid M Underhill
Jul 31, 2013·Journal of Leukocyte Biology·Irene KyrmiziIoannis Tassiulas
Mar 8, 2011·Cancer Letters·Maria VougioukalakiAristides G Eliopoulos

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