Abstract
Some reports suggest that exposure to organophosphorus (OP) pesticides increases the incidence of infections. Ethylated dialkylphosphates (EtDAPs) are metabolites of OP pesticides widely distributed with immunomodulatory potential. Chagas disease is produced by Trypanosoma cruzi parasites, and resolution of this infection requires the activation of inflammatory macrophages (MΦ), which results in cardiac fibrosis. Some reports indicate that EtDAPs increase the amount of the anti-inflammatory alternatively activated MΦ (M2; CD206+F4/80+). Therefore, we analyzed the course of T. cruzi infection, MΦ profiles from peritoneal exudate cells (PECs), inflammatory cell infiltration and fibrosis in the heart of BALB/c mice exposed to diethyldithiophosphate (DEDTP), diethylthiophosphate (DETP) or diethylphosphate (DEP, 0.01 g/kg), common DAPs produced by OP pesticides, 24 h before infection with T. cruzi. We found that DEDTP increased the parasite burden in blood by 99% at the peak of the infection and enhanced the myocardial damage due to an increase in infiltrated inflammatory cells (induced by DEDTP or DETP) and fibrosis (induced by EtDAPs). In the PECs, exposure to EtDAPs increased the proportion of the MΦ subpopulations of M2a, M2b and M2d, which are associated with tissue repair. These results indicate that exposure to EtDAPs can exacerbate the acute phase of a parasitic infection and increase the long-term damage to the heart.
Highlights
Parasite-infected individuals are continually interacting with pesticides in their environment that are known to modify some immune responses, changing the outcome of the infection and the development of the disease
We determined whether the ethylated DAPs (EtDAPs) induced a direct toxicity-inducing response to a low-virulence T. cruzi Ninoa strain; we exposed the parasites to concentrations ranging from 1 to 25 μM of DEDTP, DETP or DEP for 24 h and performed the MTT assay to evaluate the viability of the parasites
The results showed that exposure to EtDAPs did not affect the viability of the parasites by more than 20% at any concentration tested (Supplementary Fig. S1A)
Summary
Parasite-infected individuals are continually interacting with pesticides in their environment that are known to modify some immune responses, changing the outcome of the infection and the development of the disease. Several organisms can metabolize OP compounds (e.g., humans, plants, and bacteria) that are degraded by environmental factors (e.g., light, pH, and temperature), generating byproducts such as methylated or ethylated dialkylphosphates (DAPs). These ethylated DAPs (EtDAPs) are widely dispersed in the environment (e.g., food, water, soil, and air), increasing exposure to these contaminants globally in the general population, in occupationally exposed populations[14]. Some epidemiological studies report that exposure to OP pesticides may increase the rate and risk of infections in rural populations[16], exacerbating cutaneous leishmaniasis and inducing a low response to treatment in farmers exposed to chlorpyrifos, an OP pesticide that generates DETP and DEP17. In vivo studies showed that these effects on the immune response may be due to a decrease in the levels of plasma nitric oxide (NO) and interferon (IFN)-γ and to the increase in the activity of arginase, which explains the inability of macrophages (MΦ) to control the parasites or induce an adequate immune response against them[18]
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