Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2
Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2
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DOI：
10.1038/nmicrobiol.2016.54
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发表时间：
2016-06-01
影响因子：
28.3
通讯作者：
Arase, Hisashi
中科院分区：
文献类型：
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作者：
Hirayasu, Kouyuki;Saito, Fumiji;Arase, Hisashi
微生物蛋白酶降解多种宿主蛋白（1-3）。然而，微生物为什么进化成获得这样的蛋白酶以及宿主如何对微生物降解的产物做出反应在很大程度上仍然是未知的。在这里，我们已经发现，免疫球蛋白被微生物病原体破坏的白细胞免疫球蛋白样受体A2（LILRA 2），一种孤儿激活受体表达的人骨髓细胞特异性检测。来自猪鼻支原体、嗜肺军团菌、肺炎链球菌和白色念珠菌的蛋白酶切割免疫球蛋白的N-末端。乳杆菌免疫球蛋白裂解酶的鉴定。pneumophila的研究表明，该蛋白酶在一些细菌中是保守的，包括弧菌属（Vibrio spp.）和铜绿假单胞菌。这些微生物裂解的免疫球蛋白而不是正常免疫球蛋白通过LILRA 2刺激人嗜中性粒细胞。此外，通过LILRA 2刺激原代单核细胞可以抑制L.嗜肺菌小鼠感染L.在嗜肺菌中，免疫球蛋白被LILRA 2切割和识别。更重要的是，在细菌感染和刺激LILRA 2表达细胞的患者中检测到裂解的免疫球蛋白。我们的研究结果表明，LILRA 2是宿主免疫系统中的一种先天免疫受体，可检测由微生物病原体引起的免疫球蛋白异常。
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.