Paired Ig-like receptors bind to bacteria and shape TLR-mediated cytokine production.
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.
Nakayama
Masafumi
M
Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA.
Underhill
David M
DM
Petersen
Timothy W
TW
Li
Bin
B
Kitamura
Toshio
T
Takai
Toshiyuki
T
Aderem
Alan
A
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D003001:Cloning, Molecular; D016207:Cytokines / Q000378:metabolism; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008264:Macrophages / Q000276:immunology; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D011487:Protein Conformation; D011971:Receptors, Immunologic / Q000737:chemistry / Q000235:genetics / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology*; D051193:Toll-Like Receptors / Q000378:metabolism*
D016207:Cytokines; C105949:Pirb protein, mouse; D011971:Receptors, Immunologic; D051193:Toll-Like Receptors