我国斑点热立克次体感染与免疫的实验研究

Experimental studies on infection and immunity of spotted fever group rickettsiae in China

研究证明黑龙江立克次体能够感染人血管内皮细胞和BALB/c小鼠,引起小鼠菌血症和器官损伤;全基因组序列分析发现黑龙江立克次体毒力相关基因。表面蛋白质组分析鉴定了黑龙江立克次体和立氏立克次体的表面蛋白,用表面蛋白免疫C3H/HeN小鼠,发现某些表面蛋白为保护性抗原,并揭示这些保护性抗原均能够诱导抗原特异CD4+和CD8+T细胞增殖并产生和分泌IFN-γ和/或TNF-α,以及诱导高水平特异性IgG2a产生,在这些免疫因素的协同作用下使小鼠有效抵抗立克次体感染。用黑龙江立克次体感染Tim-3高表达或低表达人血管内皮细胞以及Tim-3高表达转基因小鼠,结果有力证明Tim-3高表达能够促进人血管内皮细胞和小鼠抵抗黑龙江立克次体感染。

Studies showed that Rickettsia heilongjiangensis could infect human vascular endothelial cells （ECs） and BALB/ c mice, causing bacteremia and organ damage in mice; whole genomic sequence assay revealed the virulence-associated genes of R. heilongjiangensis. The study of surface proteome identified the surface proteins of R. heilongjiangensis and R. rickettsii. By immunization of C3H/HeN mice with the surface proteins, several protective antigens were determined, which could efficiently induce proliferation and secretion of IFN-γ and/or TNF-α of in CD4 ＋ and CD8 ＋ T cells and elicited production of IgG2a in 13 cells, by which, the rickettsial organisms were eradicated in mice. We used R. heilongjiangensis to infect ECs with low expression of Tim-3 and overexpressed Tim-3 or mice with overexpressed Tim-3, our results strongly demonstrated that enhanced Tim-3 expression could inhibit rickettsial growth, both in vivo in mice and in vitro in ECs.