This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Georgel, P. Articles by Beutler, B. Search for Related Content PubMed PubMed Citation Articles by Georgel, P. Articles by Beutler, B.

 Previous Article  |  Next Article 

Infection and Immunity, August 2005, p. 4512-4521, Vol. 73, No. 8
0019-9567/05/$08.00+0     doi:10.1128/IAI.73.8.4512-4521.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

A Toll-Like Receptor 2-Responsive Lipid Effector Pathway Protects Mammals against Skin Infections with Gram-Positive Bacteria

Department of Immunology, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, California 92037,¹ Department of Pediatrics, University of California, San Diego, La Jolla, California 92093,² Department of Dermatology, Charité University Medicine Berlin, Fabeckstrasse 60-62, 14195 Berlin, Germany³

Received 26 January 2005/ Returned for modification 1 March 2005/ Accepted 10 March 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 Scd1—a gene with numerous NF-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.

Editor: F. C. Fang

This article has been cited by other articles:

• Do, T. Q., Moshkani, S., Castillo, P., Anunta, S., Pogosyan, A., Cheung, A., Marbois, B., Faull, K. F., Ernst, W., Chiang, S. M., Fujii, G., Clarke, C. F., Foster, K., Porter, E. (2008). Lipids Including Cholesteryl Linoleate and Cholesteryl Arachidonate Contribute to the Inherent Antibacterial Activity of Human Nasal Fluid. J. Immunol. 181: 4177-4187 [Abstract] [Full Text]  
• Smith, K. R., Thiboutot, D. M. (2008). Thematic review series: Skin Lipids. Sebaceous gland lipids: friend or foe?. J. Lipid Res. 49: 271-281 [Abstract] [Full Text]  
• MacDonald, M. L. E., Singaraja, R. R., Bissada, N., Ruddle, P., Watts, R., Karasinska, J. M., Gibson, W. T., Fievet, C., Vance, J. E., Staels, B., Hayden, M. R. (2008). Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice. J. Lipid Res. 49: 217-229 [Abstract] [Full Text]  
• Yu, F.-S. X., Hazlett, L. D. (2006). Toll-like Receptors and the Eye.. IOVS 47: 1255-1263 [Full Text]