Nakayama Masafumi, Underhill David M, Petersen Timothy W, Li Bin, Kitamura Toshio, Takai Toshiyuki, Aderem Alan
Institute for Systems Biology, 1441 North 34th Street, Seattle, WA 98103, USA.
J Immunol. 2007 Apr 1;178(7):4250-9. doi: 10.4049/jimmunol.178.7.4250.
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.
先天性免疫系统利用多种模式识别受体（包括Toll样受体、清道夫受体和凝集素）来识别潜在病原体。必须维持激活与抑制之间的精确平衡，以避免有害和不适当的炎症反应。在本研究中，我们鉴定出小鼠配对免疫球蛋白样受体（PIR）-B及其人类同源物免疫球蛋白样转录本2和免疫球蛋白样转录本5是金黄色葡萄球菌的新型受体。PIR-B含有四个免疫受体酪氨酸抑制基序（ITIM），被认为是一种抑制性受体。这些受体的表达使NIH3T3细胞能够结合金黄色葡萄球菌。在小鼠骨髓来源的巨噬细胞中，抗PIR单克隆抗体对PIR-B的封闭或PIR-B的基因缺失显示出对金黄色葡萄球菌的识别显著受损，以及Toll样受体介导的对该细菌的炎症反应增强。这些数据提示了配对免疫球蛋白样受体家族成员对先天性免疫调节的一种新机制。
