TH1 IN VITRO DIFFERENTIATION IS IMPAIRED BY GLYPHOSATE AND CHLORPYRIFOS BASED PESTICIDES

ORDOÑEZ, MARIA EUGENIA; GANTOV, MARIANA; LOZADA MONTANARI, BELEN; RUBINZSTEIN, NATALIA; ERRAMOUSPE, JULIETA; SIERRA, JESSICA MARIEL; SECCHIARI, FLORENCIA; REGGE, MARÍA VICTORIA; TROTTA, ALDANA; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER; FRIEDRICH, ADRIÁN

Mar del Plara

Congreso; Reunion anual de Biociencias; 2022

SAI

Chlorpyrifos (CFP) and Glyphosate (GLY) based pesticides (CbP and GbP,respectively) are widely used in agriculture. There is evidence suggesting that GbP isgenotoxic and both GbP and CbP are associated with an increased frequency ofmalignancies observed in highly fumigated rural areas. However, their effect onimmunosurveillance has been poorly explored. We have previously demonstrated thatCbP and GbP, individually, impair IFN- production by NK cells and cytotoxicity againstK562 cell line in vitro. Here, we focused on the impact of CbP, GbP and the combinationof both formulations (CbP+GbP) on the adaptive immune response. First, we developedan equi-toxic and a non-equitoxic model on Jurkat cells to determine how CbP and GbPmay interact by measuring cell death. Surprisingly, our results indicate that in bothmodels tested, CbP and GbP display an antagonistic behavior. Furthermore, weanalyzed the ability of T cells isolated from healthy donors to differentiate in vitro intothe Th1 subtype in the presence of sub-apoptotic doses of CbP, GbP and CbP+GbP.Our results show that CbP+GbP but not CbP or GbP alone decreased both T-bet andIFN- expression in CD4 + T cells evaluated by flow cytometry (p< 0,05). Moreover,CbP+GbP impact strongly on T cell proliferation capacity. Altogether, our resultsindicate that CbP+GbP but not CbP or GbP alone alter T cell function, suggesting thatboth formulations may have a cooperative effect at low doses that weaken the immunesystem´s ability to mount Th1 responses. Since the concentrations of GLY and CPFused here were far below the No-Observed Adverse Effect Level (NOAEL) for eachactive principle, this work reinforces the need of reevaluating pesticide safety usingcommercial formulations (and active principles) interactions.