Th1 in vitro differentiation is impaired by glyphosate- and chloropyrifos-based pesticides

ORDÓÑEZ, MARÍA EUGENIA; GANTOV, MARIANA; LOZADA MONTANARI, BELÉN CANDELA; RUBINSZTAIN, NATALIA; ERRAMOUSPE, JULIETA; SIERRA, JESSICA MARIEL; REGGE, MARÍA VICTORIA; SANTILLI, MARÍA CECILIA; TROTTA, ALDANA; SECCHIARI, FLORENCIA; DOMAICA, CAROLINA INÉS; FUERTES, MERCEDES BEATRIZ; ZWIRNER, NORBERTO WALTER; FRIEDRICH, ADRIÁN DAVID

Mar del Plata

Congreso; 70ª Reunión Anual de la Sociedad Argentina de Inmunología y 3rd French-Argentine Immunology Congress (FAIC); 2022

Sociedad Argentina de Inmunología

Chlorpyrifos (CFP) and Glyphosate (GLY) based pesticides (CbP and GbP, respectively) are widely used in agriculture. There is evidence suggesting that GbP is genotoxic and both GbP and CbP are associated with an increased frequency of malignancies observed in highly fumigated rural areas. However, their effect on immunosurveillance has been poorly explored. We have previously demonstrated that CbP and GbP, individually, impair IFN- production by NK cells and cytotoxicity against K562 cell line in vitro. Here, we focused on the impact of CbP, GbP and the combination of both formulations (CbP+GbP) on the adaptive immune response. First, we developed an equi-toxic and a non-equitoxic model on Jurkat cells to determine how CbP and GbP may interact by measuring cell death. Surprisingly, our results indicate that in both models tested, CbP and GbP display an antagonistic behavior. Furthermore, we analyzed the ability of T cells isolated from healthy donors to differentiate in vitro into the 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 and IFN- expression in CD4+ T cells evaluated by flow cytometry (p< 0,05). Moreover, CbP+GbP impact strongly on T cell proliferation capacity. Altogether, our results indicate that CbP+GbP but not CbP or GbP alone alter T cell function, suggesting that both formulations may have a cooperative effect at low doses that weaken the immune system´s ability to mount Th1 responses. Since the concentrations of GLY and CPF used here were far below the No-Observed Adverse Effect Level (NOAEL) for each active principle, this work reinforces the need of reevaluating pesticide safety using commercial formulations (and active principles) interactions.