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

Infect Immun. 2005 Aug;73(8):4512-21. 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). 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology
  • Chromosome Mapping
  • Eye Diseases / microbiology
  • Fatty Acids, Monounsaturated / pharmacology
  • Likelihood Functions
  • Lod Score
  • Mice
  • Mice, Inbred C57BL
  • Oleic Acid / pharmacology
  • Receptors, Immunologic / metabolism*
  • Sequence Analysis, DNA
  • Skin / immunology
  • Skin / metabolism
  • Skin / microbiology
  • Staphylococcal Skin Infections / drug therapy
  • Staphylococcal Skin Infections / immunology
  • Staphylococcal Skin Infections / metabolism*
  • Staphylococcal Skin Infections / microbiology*
  • Stearoyl-CoA Desaturase / genetics*
  • Stearoyl-CoA Desaturase / metabolism
  • Streptococcus pyogenes / drug effects
  • Streptococcus pyogenes / immunology
  • Streptococcus pyogenes / metabolism*
  • Time Factors
  • Toll-Like Receptor 2


  • Anti-Bacterial Agents
  • Fatty Acids, Monounsaturated
  • Receptors, Immunologic
  • Tlr2 protein, mouse
  • Toll-Like Receptor 2
  • palmitoleic acid
  • Oleic Acid
  • Scd1 protein, mouse
  • Stearoyl-CoA Desaturase