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.

钙在调节细胞生理和对各种病原体的免疫反应中起重要作用。我们最近的工作强调了钙稳态在各种感染过程中在树突状细胞和巨噬细胞中的关键作用。在这里，我们研究了钙稳态在分枝杆菌感染过程中调节T细胞活化和功能的作用。结果表明，钙稳态在分枝杆菌感染过程中具有调节T细胞活化和功能的多种作用。这包括调节共刺激分子的表达，细胞因子谱和效应子功能。观察到电压门控钙通道（VGCC）的净负作用。在分枝杆菌引发的T细胞中抑制VGCC诱导了促炎性细胞因子的产生增加以及效应子表型增加。当感染的巨噬细胞与VGCC抑制的T细胞一起孵育时，诱导巨噬细胞上共刺激分子表达的表达增加，促炎细胞因子的产生增加，自噬和凋亡增加。这共同导致巨噬细胞内分枝杆菌的存活减少。数据表明，通过钙流入和释放介导病原体存活或清除的途径，可以很好地调节保护性反应。