Complement C3aR/C5aR-binding protein Suilysin of Streptococcus suis contributes to monocyte chemotaxis
Complement C3aR/C5aR-binding protein Suilysin of Streptococcus suis contributes to monocyte chemotaxis
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DOI：
10.1016/j.vetmic.2020.108599
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发表时间：
2020-03-01
影响因子：
3.3
通讯作者：
Zhou, Rui
中科院分区：
文献类型：
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作者：
Deng, Simin;Zhao, Liyang;Zhou, Rui
猪链球菌是一种引起猪和人类严重感染和猝死的新型病原体。在感染过程中，补体C3 a和C5 a被报道通过其相应的受体C3 aR和C5 aR诱导免疫细胞朝向感染和损伤部位。然而，S。C3 aR和C5 aR介导猪逃避免疫监视的机制尚不清楚。在这项研究中，我们分析和构建一个S。猪细菌双杂交猎物文库，包含39个LPXTG锚定蛋白和18个分泌蛋白。通过细菌双杂交技术鉴定了两个可能与C3 aR结合的蛋白：巯基激活毒素Suilysin、RTX家族胞外蛋白A基因和三个可能与C5 aR结合的蛋白：巯基激活毒素Suilysin、5 ′-核苷酸酶和枯草杆菌蛋白酶样丝氨酸蛋白酶。Far-western印迹分析证实胆固醇结合溶细胞素Suilysin可以与C3 aR和C5 aR两者相互作用。趋化性实验表明，重组和天然Suilysin可以抑制由C3 a和C5 a介导的单核细胞趋化性。这些发现扩大了我们对猪链球菌溶血素生物学意义的认识，并为猪链球菌溶血素的研究提供了新的视角。猪补体逃避。
Streptococcus suis is an emerging swine and human pathogen causing severe infections and sudden death. During infection, complement C3a and C5a were reported to induce immune cells towards infection and injury sites via their corresponding receptors C3aR and C5aR. However, how S. suis evade immune surveillance mediated by C3aR and C5aR remains unclear. In this study, we analyze and construct an S. suis bacterial two-hybrid prey library containing 39 LPXTG motif anchored proteins and 18 secreted proteins. Two highly possible C3aR-binding proteins: thiol-activated toxin Suilysin, putative RTX family exoprotein A gene and three highly possible C5aR-binding proteins: thiol-activated toxin Suilysin, putative 5'-nucleotidase and subtilisin-like serine protease are identified through bacterial two-hybrid assay. Far-western blot assay confirms that a cholesterol-binding cytolysin Suilysin can interact with both C3aR and C5aR. Chemotaxis assays demonstrate that recombinant and natural Suilysin can inhibit monocyte chemotaxis mediated by C3a and C5a. These findings enlarge our knowledge of suilysin biological significance and provide a new perspective on S. suis complement evasion.