Mycobacterium tuberculosis PE_PGRS41 Enhances the Intracellular Survival of M. smegmatis within Macrophages Via Blocking Innate Immunity and Inhibition of Host Defense.
Mycobacterium tuberculosis PE_PGRS41 Enhances the Intracellular Survival of M. smegmatis within Macrophages Via Blocking Innate Immunity and Inhibition of Host Defense.
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结核分枝杆菌 PE_PGRS41 通过阻断先天免疫和抑制宿主防御来增强巨噬细胞内耻垢分枝杆菌的细胞内存活
DOI：
10.1038/srep46716
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发表时间：
2017-04-25
影响因子：
4.6
通讯作者：
Xie J
中科院分区：
文献类型：
--
作者：
Deng W;Long Q;Zeng J;Li P;Yang W;Chen X;Xie J
结核分枝杆菌（M.结核病）作为病原体的感染在很大程度上有助于其操纵宿主免疫应答的能力。分枝杆菌基因组结核分枝杆菌编码多种免疫调节蛋白，包括多基因PE_PPE家族的几个成员。尽管有大量的研究，但PE_PGRS蛋白在分枝杆菌发病机制中的作用仍不清楚。M.结核PE_PGRS 41，其特征在于一个扩展的和独特的C-末端结构域。在非致病性的耻垢分枝杆菌中表达PE_PGRS 41，其通过改变细胞壁的完整性而严重损害重组体对多种胁迫的抗性。感染M.携带PE_PGRS 41的耻垢病减少TNF-α、IL-1β和IL-6的产生。此外，PE_PGRS 41促进了M.巨噬细胞内的smeglycin通过抑制细胞凋亡和自噬而增强细胞毒性细胞死亡。这些结果表明PE_PGRS 41是M.结核病和足以赋予致病特性的M。恶臭
The success of Mycobacterium tuberculosis (M. tuberculosis) as a pathogen is largely contributes to its ability to manipulate the host immune responses. The genome of M. tuberculosis encodes multiple immune-modulatory proteins, including several members of the multi-genic PE_PPE family. Despite of intense research, the roles of PE_PGRS proteins in mycobacterial pathogenesis remain elusive. The function of M. tuberculosis PE_PGRS41, characterized by an extended and unique C-terminal domain, was studied. Expression of PE_PGRS41 in Mycobacterium smegmatis, a non-pathogenic species intrinsically deficient of PE_PGRS, severely impaired the resistance of the recombinant to multiple stresses via altering the cell wall integrity. Macrophages infected by M. smegmatis harboring PE_PGRS41 decreased the production of TNF-α, IL-1β and IL-6. In addition, PE_PGRS41 boosted the survival of M. smegmatis within macrophage accompanied with enhanced cytotoxic cell death through inhibiting the cell apoptosis and autophagy. Taken together, these results implicate that PE_PGRS41 is a virulence factor of M. tuberculosis and sufficient to confer pathogenic properties to M. smegmatis.