Abstract
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.
Highlights
The Leishmania species are obligate intracellular protozoa of the kinetoplastids family that cause various clinical manifestations of leishmaniasis
Most of the previous studies did not show the pathophysiological relevance of the arsenic exposure related changes in Leishmania parasites and their host cells, the pathophysiological consequences of arsenic related to visceral leishmaniasis (VL) and other infectious diseases are still remain poorly understood
The experiment was initiated to examine the impact of arsenic exposure on infectivity and viability of Leishmania parasite using microscopic and MTT assay techniques respectively
Summary
The Leishmania species are obligate intracellular protozoa of the kinetoplastids family that cause various clinical manifestations of leishmaniasis. The widespread distribution of arsenic in the ground water of VL endemic areas is one of the major contributing factors to antimony resistance [6]. Arsenic is a highly toxic metalloid, released into the water of Indian subcontinent, and its co-existence with antimony resistance in the VL endemic area of Bihar, India has led to multiple challenges for public health [7,8]. It has previously been reported that the level of thiol has been increased several fold in arsenic-exposed and antimonyresistant Leishmania parasites that bind to and are sequestered in intracellular vesicles [13,14]. The metalloid lowers the rate of the Krebs cycle and alters the expression of most of the mitochondrial enzymes to depolarize the membrane potential and cause oxidative phosphorylation [15,16]
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