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Molecular and Cellular Biology, September 2004, p. 7949-7957, Vol. 24, No. 18
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.18.7949-7957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Innate Immune Responses in Peptidoglycan Recognition Protein L-Deficient Mice

Min Xu, Zhien Wang, and Richard M. Locksley*

Howard Hughes Medical Institute, Departments of Medicine and Microbiology/Immunology, University of California San Francisco, San Francisco, California

Received 16 April 2004/ Returned for modification 1 May 2004/ Accepted 17 June 2004

Peptidoglycan recognition proteins (PGRPs) constitute a family of innate immune recognition molecules. In Drosophila, distinct PGRPs bind to peptidoglycans on gram-positive or gram-negative bacteria and provide essential signals upstream of the Toll and Imd pathways required for immunity against infection. Four PGRPs, PGRP-L, -S, -I{alpha}, and -Iß, are expressed from three genes in mammals. In this paper, we provide direct evidence that the longest family member, PGRP-L, is a secreted serum protein with the capacity to multimerize. Using gene targeting to create PGRP-L-deficient mice, we demonstrate little contribution by PGRP-L to systemic challenge using gram-negative bacteria (Escherichia coli, slightly less susceptible), Gram-positive bacteria (Staphylococcus aureus), or yeast (Candida albicans). Peritoneal macrophages from PGRP-L-deficient mice produced decreased amounts of the inflammatory cytokines interleukin 6 and tumor necrosis factor alpha when stimulated with E. coli or lipopolysaccharide, but comparable amounts when stimulated with S. aureus, C. albicans, or their cell wall components. Additionally, these cells produced similar amounts of cytokines when challenged with gram-positive or -negative peptidoglycans. In contrast to its critical role in immunity in flies, PGRP-L is largely dispensable for mammalian immunity against bacteria and fungi.

* Corresponding author. Mailing address: University of California San Francisco, 521 Parnassus Ave., Room C-443, San Francisco, CA 94143-0654. Phone: (415) 476-5859. Fax: (415) 476-9364. E-mail: locksley{at}medicine.ucsf.edu.

Molecular and Cellular Biology, September 2004, p. 7949-7957, Vol. 24, No. 18
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.18.7949-7957.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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