Nature子刊发现对抗微生物病原体的新防御机制
2016/7/14 6:48:08Nature Microbiol 世界医疗科技资讯

    

     研究人员首次发现一个能够检测到病原微生物入侵的人类免疫受体。因此他们成功发现一条至今未知的宿主防御机制。这些结果将促进未来开发预防和治疗传染病的新方法。

     传染病是全世界都存在的一个严重问题，是导致人类死亡的一个重要原因。传染病的发生主要由破坏宿主生物防御系统的病原体微生物引起，这些病原微生物能够产生多种蛋白。但是人们对于宿主生物防御系统的多种机制仍了解较少。

     来自日本的科学家发现一些类型的微生物体通过产生破坏蛋白的蛋白酶入侵免疫系统，这样免疫系统产生的抗体就无法触发宿主的免疫应答。通过研究他们进一步发现了一种能够识别切割后抗体的未知受体分子，该分子能够帮助对抗病原微生物的免疫入侵机制。

    

     研究人员在对受到支原体感染的人类细胞进行分析时发现了这种叫做LILRA2的受体分子。除了支原体以外，其他一些病原微生物比如军团杆菌(寄生在细胞中会引起肺炎)，肺炎球菌和流感嗜血杆菌(这两种细菌都会引起肺炎和中耳炎)以及念珠菌(一种正常存在于口腔或阴道中的真菌，在机体免疫功能下降的时候可能引起感染)也会产生蛋白酶对抗体进行切割。以军团杆菌为例，军团杆菌会感染免疫细胞并进行复制，研究表明当LILRA2识别到切割后的抗体时会对军团杆菌的生长进行抑制。除此之外，在其他受到细菌感染的部位表达LILRA2的细胞也会发生激活。

     LILRA2免疫受体能够介导一种生物学防御系统对抗病原体微生物，该发现有助于开发预防和治疗传染病的新方法，比如开发调节LILRA2功能的药物和疫苗。

     原文阅读

     Microbially cleaved immunoglobulins are sensed by the innate immune receptor LILRA2

     Nature Microbiology 1, Article number: 16054 (2016)

     doi:10.1038/nmicrobiol.2016.54

     Kouyuki Hirayasu, Fumiji Saito, Tadahiro Suenaga, Kyoko Shida, Noriko Arase, Keita Oikawa, Toshifumi Yamaoka, Hiroyuki Murota, Hiroji Chibana, Ichiro Nakagawa, Tomoko Kubori, Hiroki Nagai, Yuji Nakamaru, Ichiro Katayama, Marco Colonna & Hisashi Arase

     Microbial proteases degrade a variety of host proteins1, 2, 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.

    

     长按二维码扫描关注

    http://weixin.100md.com
返回 世界医疗科技资讯 返回首页 返回百拇医药