本文研究发现，可以采用一种在人类骨髓细胞中表达的孤儿激活受体——白细胞免疫球蛋白样受体A2（LILRA2）特异性检测病原微生物对免疫球蛋白的破坏。研究利用猪鼻支原体、嗜肺性军团病杆菌、肺炎链球菌和白念珠菌蛋白酶水解免疫球蛋白氮末端。对嗜肺性军团病杆菌蛋白酶水解免疫球蛋白的鉴定结果表明，蛋白酶可以穿透弧菌属和绿脓杆菌等部分细菌。这些微生物水解免疫球蛋白并不是普通的免疫球蛋白，而是可以通过LILRA2刺激人类中性细胞的生成。另外，通过LILRA2刺激原核细胞生成可以抑制嗜肺性军团病杆菌的生长。小鼠感染嗜肺性军团病杆菌后，免疫球蛋白被水解，并可以被LILRA2识别。更重要的是，在受到细菌感染的病人体内检测到了水解免疫球蛋白，这一类免疫球蛋白促进了LILRA2表达细胞的生成。本研究阐明，LILRA2是一种存在于宿主免疫系统的天然免疫受体，可以检测由病原微生物引起的免疫球蛋白异常。
外文摘要：Microbial proteases degrade a variety of host proteins(1-3). However, it has remained largely unknown why microorganisms have evolved to acquire such proteases and how the host responds to microbially degraded products. Here, we have found that immunoglobulins disrupted by microbial pathogens are specifically detected by leukocyte immunoglobulin-like receptor A2 (LILRA2), an orphan activating receptor expressed on human myeloid cells. Proteases from Mycoplasma hyorhinis, Legionella pneumophila, Streptococcus pneumonia and Candida albicans cleaved the N-terminus of immunoglobulins. Identification of the immunoglobulin-cleaving protease from L. pneumophila revealed that the protease is conserved across some bacteria including Vibrio spp. and Pseudomonas aeruginosa. These microbially cleaved immunoglobulins but not normal immunoglobulins stimulated human neutrophils via LILRA2. In addition, stimulation of primary monocytes via LILRA2 inhibited the growth of L. pneumophila. When mice were infected with L. pneumophila, immunoglobulins were cleaved and recognized by LILRA2. More importantly, cleaved immunoglobulins were detected in patients with bacterial infections and stimulated LILRA2-expressing cells. Our findings demonstrate that LILRA2 is a type of innate immune receptor in the host immune system that detects immunoglobulin abnormalities caused by microbial pathogens.
作者：Hirayasu K；Saito F；Suenaga T等，
作者单位：日本大阪大学
期刊名称：NATURE MICROBIOLOGY
期刊影响因子：0.0
出版年份：2016
出版刊次：7
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