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Deciphering the role of calcium homeostasis in T cells functions during mycobacterial infection

机译:在分枝杆菌感染期间解入钙稳态术中钙稳态的作用

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Calcium plays an important role in regulating cell physiology and immune responses to various pathogens. Our recent work has highlighted the crucial role for calcium homeostasis in dendritic cells and macrophages during various infections. Here we investigated the effect of calcium homeostasis in regulating T cell activation and function during mycobacterial infection. Results show that calcium homeostasis had varied effects in regulating T cell activation and function during mycobacterial infection. This included regulation of the expression of co-stimulatory molecules, cytokine profiles and effector function. A net negative role for Voltage Gated Calcium Channel (VGCC) was observed. Inhibiting VGCC in mycobacteria primed T cells induced increased production of pro-inflammatory cytokines and an increased effector phenotype. Infected macrophages when incubated with VGCC inhibited T cells, induced increased expression of co-stimulatory molecule expression on macrophages, increased the production of pro-inflammatory cytokines and increased autophagy and apoptosis. This collectively led to reduced survival of mycobacteria inside macrophages. The data point towards a fine regulation of protective responses by routes of calcium influx and release that mediate pathogen survival or clearance.
机译:钙在调节细胞生理和对各种病原体的免疫反应中起着重要作用。我们最近的工作强调了钙稳态在树突状细胞和巨噬细胞在各种感染中的关键作用。在这里,我们研究了在分枝杆菌感染期间钙稳态在调节T细胞活化和功能中的作用。结果表明,在分枝杆菌感染期间,钙稳态在调节T细胞活化和功能方面具有不同的作用。这包括调节共刺激分子的表达、细胞因子谱和效应器功能。观察到电压门控钙通道(VGCC)的净负作用。在分枝杆菌诱导的T细胞中抑制VGC可诱导促炎细胞因子的产生增加和效应表型的增加。当感染的巨噬细胞与VGC孵育时,抑制T细胞,诱导巨噬细胞上共刺激分子表达增加,增加促炎细胞因子的产生,并增加自噬和凋亡。这共同导致巨噬细胞内分枝杆菌的存活率降低。数据表明,通过调节病原体存活或清除的钙内流和释放途径,对保护性反应进行精细调节。

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