Paired Ig-Like Receptors Bind to Bacteria and Shape TLR-Mediated Cytokine Production

DOI PDF 10 Citations
  • Masafumi Nakayama
    *Institute for Systems Biology, Seattle, WA 98103;
  • David M. Underhill
    †Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048;
  • Timothy W. Petersen
    *Institute for Systems Biology, Seattle, WA 98103;
  • Bin Li
    *Institute for Systems Biology, Seattle, WA 98103;
  • Toshio Kitamura
    ‡Divisions of Cellular Therapy and Hematopoietic Factors, Institute of Medical Science, University of Tokyo, Tokyo, Japan; and
  • Toshiyuki Takai
    §Department of Experimental Immunology, Institute of Development, Aging, and Cancer, Tohoku University, Sendai, Japan
  • Alan Aderem
    *Institute for Systems Biology, Seattle, WA 98103;

Abstract

<jats:title>Abstract</jats:title> <jats:p>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.</jats:p>

Journal

  • The Journal of Immunology

    The Journal of Immunology 178 (7), 4250-4259, 2007-04-01

    The American Association of Immunologists

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