Neumann Ariane, Happonen Lotta, Karlsson Christofer, Bahnan Wael, Frick Inga-Maria, Björck Lars
Division of Infection Medicine, Department of Clinical Sciences, BMC, Lund University, 22184, Lund, Sweden.
iScience. 2021 Mar 20;24(4):102339. doi: 10.1016/j.isci.2021.102339. eCollection 2021 Apr 23.
is a major bacterial pathogen in the human population and isolates of the clinically important M1 serotype secrete protein Streptococcal inhibitor of complement (SIC) known to interfere with human innate immunity. Here we find that SIC from M1 bacteria interacts with TLR2 and CD14 on monocytes leading to the activation of the NF-κB and p38 MAPK pathways and the release of several pro-inflammatory cytokines (e.g. TNFα and INFγ). In human plasma, SIC binds clusterin and histidine-rich glycoprotein, and whole plasma, and these two purified plasma proteins enhanced the activation of monocytes by SIC. Isolates of the M55 serotype secrete an SIC homolog, but this protein did not activate monocytes. M1 isolates are common in cases of invasive infections characterized by massive inflammation, and the results of this study indicate that the pro-inflammatory property of SIC contributes to the pathology of these severe clinical conditions.
是人类主要的细菌病原体，临床上重要的M1血清型菌株分泌的蛋白——补体链球菌抑制剂（SIC），已知其会干扰人类先天免疫。在此我们发现，来自M1细菌的SIC与单核细胞上的TLR2和CD14相互作用，导致NF-κB和p38丝裂原活化蛋白激酶（MAPK）途径的激活以及几种促炎细胞因子（如TNFα和INFγ）的释放。在人血浆中，SIC与簇集素和富含组氨酸的糖蛋白以及全血浆结合，并且这两种纯化的血浆蛋白增强了SIC对单核细胞的激活作用。M55血清型菌株分泌一种SIC同源物，但这种蛋白不会激活单核细胞。M1菌株在以大量炎症为特征的侵袭性感染病例中很常见，本研究结果表明，SIC的促炎特性促成了这些严重临床病症的病理过程。
