生物
TLR2型
效应器
先天免疫系统
免疫系统
微生物学
Toll样受体
金黄色葡萄球菌
化脓性链球菌
受体
病原相关分子模式
基因
细菌
免疫学
模式识别受体
遗传学
作者
Philippe Georgel,Karine Crozat,Xavier Lauth,Evgenia Makrantonaki,Holger Seltmann,Sosathya Sovath,Kasper Hoebe,Xin Du,Sophie Rutschmann,Zhengfan Jiang,Timothy D. Bigby,Victor Nizet,Christos C. Zouboulis,Bruce Beutler
标识
DOI:10.1128/iai.73.8.4512-4521.2005
摘要
flake (flk), an N-ethyl-N-nitrosourea-induced recessive germ line mutation of C57BL/6 mice, impairs the clearance of skin infections by Streptococcus pyogenes and Staphylococcus aureus, gram-positive pathogens that elicit innate immune responses by activating Toll-like receptor 2 (TLR2). Positional cloning and sequencing revealed that flk is a novel allele of the stearoyl coenzyme A desaturase 1 gene (Scd1). flake homozygotes show reduced sebum production and are unable to synthesize the monounsaturated fatty acids (MUFA) palmitoleate (C(16:1)) and oleate (C(18:1)), both of which are bactericidal against gram-positive (but not gram-negative) organisms in vitro. However, intradermal MUFA administration to S. aureus-infected mice partially rescues the flake phenotype, which indicates that an additional component of the sebum may be required to improve bacterial clearance. In normal mice, transcription of Scd1-a gene with numerous NF-kappaB elements in its promoter--is strongly and specifically induced by TLR2 signaling. Similarly, the SCD1 gene is induced by TLR2 signaling in a human sebocyte cell line. These observations reveal the existence of a regulated, lipid-based antimicrobial effector pathway in mammals and suggest new approaches to the treatment or prevention of infections with gram-positive bacteria.
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