Division of Microbiology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences (Indian Council of Medical Research), Agamkuan, Patna, Bihar, India.
PLoS One. 2019 Feb 5;14(2):e0210737. doi: 10.1371/journal.pone.0210737. eCollection 2019.
The arsenic contamination of ground water in visceral leishmaniasis (VL) endemic areas in Bihar, India leads to human exposure through drinking water. Possibly, the consumed arsenic (As) accumulates in the tissues of VL patients, who subsequently internalize intracellular amastigotes to confer resistance against chemotherapy to the parasite, leading to modulation in the host's immune response. This hypothesis appears to be consistent with the in vitro findings that in arsenic-exposed parasites, the mitochondrial membrane potential became depolarized, whereas the reduced thiol and lactate production was overexpressed with enhanced glucose consumption; therefore, the reduced thiol possibly supports an immunosuppressive state in the host cells. This observation was well supported by the down-regulated expression of pro-inflammatory cytokines (IL-2, IL-12, IFN-γ, and TNF-α) with a suppressed anti-leishmanial function of macrophage (NO, ROS). In contrast, the pathophysiological mechanism of VL has received ample support by the promotion of Th2 cytokines (IL-4 and IL-10) in the presence of arsenic-exposed Leishmania parasites (LdAS). Dysfunction of mitochondria and the overexpression of lactate production raise the possibility of the Warburg effect being operative through the up-regulation of glucose consumption by parasites to enhance the energy production, possibly augmenting virulence. Therefore, we surmise from our data that arsenic exposure to Leishmania donovani modulates the immune response and infection pattern by impairing parasite function, which may affect the anti-leishmanial effect in VL.
印度比哈尔邦内脏利什曼病（VL）流行地区的地下水砷污染通过饮用水导致人类暴露。可能是摄入的砷（As）在 VL 患者的组织中积累，随后这些患者将细胞内无鞭毛体内化，从而对寄生虫产生抗化疗抗性，导致宿主免疫反应的调节。这一假说似乎与体外研究结果一致，即在砷暴露的寄生虫中，线粒体膜电位去极化，而还原型硫醇和乳酸产量过度表达，同时葡萄糖消耗增加；因此，还原型硫醇可能支持宿主细胞中的免疫抑制状态。这种观察结果得到了很好的支持，即促炎性细胞因子（IL-2、IL-12、IFN-γ 和 TNF-α）的下调表达与巨噬细胞（NO、ROS）的抗利什曼原虫功能受到抑制有关。相比之下，VL 的病理生理机制得到了充分的支持，即在砷暴露的利什曼原虫（LdAS）存在的情况下，Th2 细胞因子（IL-4 和 IL-10）的促进。线粒体功能障碍和乳酸产量的过度表达增加了寄生虫通过上调葡萄糖消耗来增强能量产生的可能性，从而增强毒力，可能导致沃伯格效应。因此，根据我们的数据，砷暴露于利什曼原虫会通过损害寄生虫功能来调节免疫反应和感染模式，这可能会影响 VL 中的抗利什曼原虫效果。
