Mycobacterium tuberculosis (M. tb), the intracellular pathogen causing tuberculosis, has developed mechanisms that endow infectivity and allow it to modulate host immune response for its survival. Genomic and proteomic analyses of non-pathogenic and pathogenic mycobacteria showed presence of genes and proteins that are specific to M. tb. In silico studies predicted that M.tb Rv1954A is a hypothetical secretory protein that exhibits intrinsically disordered regions and possess B cell/T cell epitopes. Treatment of macrophages with Rv1954A led to TLR4-mediated activation with concomitant increase in secretion of pro-inflammatory cytokines, IL-12 and TNF-α. In vitro studies showed that rRv1954A protein or Rv1954A knock-in M. smegmatis (Ms_Rv1954A) activates macrophages by enhancing the expression of CD80 and CD86. An upregulation in the expression of CD40 and MHC I/II was noted in the presence of Rv1954A, pointing to its role in enhancing the association of APCs with T cells and in the modulation of antigen presentation, respectively. Ms_Rv1954A showed increased infectivity, induction of ROS and RNS, and apoptosis in RAW264.7 macrophage cells. Rv1954A imparted protection against oxidative and nitrosative stress, thereby enhancing the survival of Ms_Rv1954A inside macrophages. Mice immunized with Ms_Rv1954A showed that splenomegaly and primed splenocytes restimulated with Rv1954A elicited a Th1 response. Infection of Ms_Rv1954A in mice through intratracheal instillation leads to enhanced infiltration of lymphocytes in the lungs without formation of granuloma. While Rv1954A is immunogenic, it did not cause adverse pathology. Purified Rv1954A or Rv1954A knock-in M. smegmatis (Ms_Rv1954A) elicited a nearly two-fold higher titer of IgG response in mice, and PTB patients possess a higher IgG titer against Rv1954A, also pointing to its utility as a diagnostic marker for TB. The observed modulation of innate and adaptive immunity renders Rv1954A a vital protein in the pathophysiology of this pathogen.

结核分枝杆菌 （结核分枝杆菌）（一种引起结核的细胞内病原体）已经开发出赋予传染性并使其能够调节宿主免疫应答以维持生存的机制。对非致病性和致病性分枝杆菌的基因组和蛋白质组学分析显示，存在针对特定分枝杆菌的基因和蛋白质结核分枝杆菌。 电脑 研究预测 结核菌Rv1954A是一种假设的分泌蛋白，具有固有的无序区域并具有B细胞/ T细胞表位。用Rv1954A处理巨噬细胞导致TLR4介导的活化，同时促炎性细胞因子，IL-12和TNF-α的分泌增加。体外 研究表明，rRv1954A蛋白或Rv1954A敲入 耻垢分枝杆菌（Ms_Rv1954A）通过增强CD80和CD86的表达来激活巨噬细胞。在Rv1954A的存在下，CD40和MHC I / II的表达上调，表明其分别在增强APC与T细胞的缔合和调节抗原呈递中的作用。Ms_Rv1954A在RAW264.7巨噬细胞中显示出更高的感染力，ROS和RNS的诱导以及细胞凋亡。Rv1954A赋予了抵抗氧化和亚硝化应激的保护，从而提高了Ms_Rv1954A在巨噬细胞内部的存活率。用Ms_Rv1954A免疫的小鼠显示，用Rv1954A重新刺激的脾肿大和初免的脾细胞引起Th1反应。通过气管内滴注在小鼠中感染Ms_Rv1954A会导致肺中淋巴细胞的浸润增强，而不会形成肉芽肿。尽管Rv1954A具有免疫原性，但并未引起不良病理。纯化的Rv1954A或Rv1954A敲入耻垢分枝杆菌（Ms_Rv1954A）在小鼠中引起的IgG滴度几乎提高了两倍，而PTB患者对Rv1954A的IgG滴度更高，也指出了其作为结核病诊断标志物的效用。观察到的先天性和适应性免疫的调节使Rv1954A在该病原体的病理生理学中成为重要蛋白。