Streptococcus pneumoniae is a Gram-positive pathogen with high morbidity and mortality globally but some of its pathogenesis remains unknown. Previous research has provided evidence that aminopeptidase N (PepN) is most likely a virulence factor of S. pneumoniae. However, its role in S. pneumoniae virulence and its interaction with the host remains to be confirmed. We generated a pepN gene deficient mutant strain and found that its virulence for mice was significantly attenuated as were in vitro adhesion and invasion of host cells. The PepN protein could induce a strong innate immune response in vivo and in vitro and induced secretion of IL-6 and TNF-α by primary peritoneal macrophages via the rapid phosphorylation of MAPK and PI3K/AKT signaling pathways and this was confirmed using specific pathway inhibitors. In conclusion, PepN is a novel virulence factor that is essential for the virulence of S. pneumoniae and induces host innate immunity via MAPK and PI3K/AKT signaling.

中文翻译：

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肺炎链球菌氨肽酶N通过MAPK和PI3K / AKT信号传导增强细菌的毒力并引起强烈的先天免疫应答

肺炎链球菌是一种革兰氏阳性病原体，在全球具有高发病率和高死亡率，但其某些发病机理仍然未知。先前的研究提供了证据，表明氨肽酶N（PepN）最有可能是肺炎链球菌的致病因子。然而，其在肺炎链球菌毒力中的作用及其与宿主的相互作用仍有待证实。我们产生了pepN基因缺陷型突变株，并发现其对小鼠的毒力显着减弱，在体外粘附和侵袭宿主细胞也是如此。PepN蛋白可以在体内和体外诱导强烈的先天免疫应答并通过MAPK和PI3K / AKT信号通路的快速磷酸化诱导初级腹膜巨噬细胞分泌IL-6和TNF-α，这一点已通过特异性通路抑制剂加以证实。总之，PepN是一种新型毒力因子，对于肺炎链球菌的毒力至关重要，并通过MAPK和PI3K / AKT信号传导诱导宿主先天免疫。