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* Institute for Systems Biology, Seattle, WA 98103;
Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
Divisions of Cellular Therapy and Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
Department of Experimental Immunology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
The innate immune system uses a wide variety of pattern recognition receptors including TLRs, scavenger receptors, and lectins to identify potential pathogens. A carefully regulated balance between activation and inhibition must be kept to avoid detrimental and inappropriate inflammatory responses. In this study, we identify murine-paired Ig-like receptor (PIR)-B, and its human orthologs Ig-like transcript 2 and Ig-like transcript 5 as novel receptors for Staphylococcus aureus. PIR-B contains four ITIM motifs and is thought to be an inhibitory receptor. Expression of these receptors enables NIH3T3 cells to bind S. aureus. In mouse bone marrow-derived macrophages, masking of PIR-B by anti-PIR mAb or genetic deletion of PIR-B shows significantly impaired recognition of S. aureus and enhanced TLR-mediated inflammatory responses to the bacteria. These data suggest a novel mechanism for innate immune regulation by paired Ig-like receptor family members.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the National Institutes of Health. M.N. was supported by a postdoctoral fellowship from Uehara Memorial Foundation.
2 Current address: Cytopeia Incorporated, 12730 28th Avenue Northeast, Seattle, WA 98125.
3 Address correspondence and reprint requests to Dr. Alan Aderem, Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103. E-mail address: aderem{at}systemsbiology.org
4 Abbreviations used in this paper: PIR, paired Ig-like receptor; DC, dendritic cell; ILT, Ig-like transcript; LILR, leukocyte Ig-like receptor; TRITC, tetramethylrhodamine isothiocyanate; WT, wild type.
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