The myobacterial factors and the associated mechanism by which Mycobacterium tuberculosis (Mtb) evades the host immune surveillance system remain widely unexplored. Here, we found that overexpressing Rv1016c, a mannosylated protein of M. tuberculosis in BCG (rBCG-Rv1016c) led to increased virulence of the recombined BCG in the severe-combined immunodeficient (SCID) mice model and to a loss of protective efficacy in a zebrafish-M. marinum model, compared to wild type BCG. Further investigations on the effects of rBCG-Rv1016c on the host innate immunity revealed that rBCG-Rv1016c decreased the production of cytokines IL-2, IL-12p70, TGF-β, IL-6 as well as of the co-stimulatory molecules CD80, CD86, MHC-I and MHC-II by the infected DCs. These effects were mimicked by rBCG-Rv1016cHis, which carried an extra 6-His tag at the C-terminus of Rv1016c. Relatively to BCG infected DCs, the rBCG-Rv1016c-infected DCs failed to polarize naïve T cells to Th1- and Th17-type cells to secret IFN-γ and IL-17. Additionally, T lymphocytes from BCG- infected mice showed significantly less proliferation and production of IFN-γ and IL-17. Similarly, rBCG-Rv1016c mice released a higher level of IL-10 in response to rBCG-Rv1016c stimulation than wild type BCG infected mice. Furthermore, DCs from TLR-2 knockout mice showed no reduction in IL-6, IL-12 p70 and TGF-β secretion in response to rBCG-Rv1016c infection, compared to DCs infected with BCG. We propose that Rv1016c interferes in differentiation of the DCs by targeting suppressor of cytokine signaling (SOCS) 1 and SOCS3 expression, which subsequently leads to the reduction in STAT-1 and STAT-6 phosphorylation. These findings open new perspectives regarding the immunosuppressive strategies adopted by Mtb to survive in the host.Keywords: Dendritic cell; Glycosylated protein; Mycobacterium tuberculosis; Th1 cell response; Th17 cell response; Tuberculosis.

---

 

乐备实是国内专注于提供高质量蛋白检测以及组学分析服务的实验服务专家，自2018年成立以来，乐备实不断寻求突破，公司的服务技术平台已扩展到单细胞测序、空间多组学、流式检测、超敏电化学发光、Luminex多因子检测、抗体芯片、PCR Array、ELISA、Elispot、PLA蛋白互作、多色免疫组化、DSP空间多组学等30多个，建立起了一套涵盖基因、蛋白、细胞以及组织水平实验的完整检测体系。

 
我们可提供从样本运输、储存管理、样本制备、样本检测到检测数据分析的全流程服务。凭借严格的实验室管理流程、标准化实验室操作、原始数据储存体系以及实验项目管理系统，已经为超过3000家客户单位提供服务，年检测样本超过100万，受到了广大客户的信任与支持。