A Toll-like receptor 2-responsive lipid effector pathway protects mammals against skin infections with gram-positive bacteria

作者：Georgel P; Crozat K; Lauth X; Makrantonaki E; Seltmann H; Sovath S; Hoebe K; Du X; Rutschmann S; Jiang ZF; Bigby T; Nizet V; Zouboulis CC; Beutler B^*

来源：Infection and Immunity, 2005, 73(8): 4512-4521.

DOI：10.1128/IAI.73.8.4512-4521.2005

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) (K. Takeda and S. Akira, Cell. Microbiol. 5:143-153, 2003). 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 Sed1-a gene with numerous NF-kappa B 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.

• 出版日期2005-8