EFFECT OF PGE2 ON THE FUNCTIONS OF NEUTROPHILS DURING HUMAN TUBERCULOSIS

MARIA PAULA MORELLI; LORENA CIALLELLA; JOAQUIN M. PELLEGRINI; NICOLÁS O. AMIANO; VERÓNICA E. GARCIA; CANDELA MARTIN; NANCY TATEOSIAN; DOMINGO J. PALMERO

Buenos Aires

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Neutrophils have been associated with tuberculosis (TB) protection but also with excessive inflammatory burden. Previously we showed that PGE2 decreased CD11b expression in Mtb-Ag stimulated neutrophils from healthy donors (HD). Here we investigated the potential role of PGE2 on human neutrophils´ response during active TB. We evaluated the expression of immunoreceptors (PD-L1, PD-L2), the generation of reactive oxygen species (ROS) and the induction of autophagy.Neutrophils were obtained from heparinized peripheral blood from HD and tuberculosis patients (TB) and cultured (2x106cells/ml) with a Mycobacterium tuberculosis lysate (Mtb-Ag, 10μg/ml) ± PGE2 (2μM). ROS production and PD-L1/PD-L2 surface expression were determined by flow cytometry. Confocal microscopy and flow cytometry were used to evaluate autophagy levels. P-values < 0,05 were considered significantly different.We found that Mtb-Ag stimulation increased PD-L1 expression on neutrophils from HD (p=0,041, Ag-stimulated vs. unstimulated neutrophils) and PGE2 decreased it (p=0,041). Additionally, we measured significantly lower PD-L1 levels on Mtb-Ag stimulated neutrophils from TB patients than on HD´s stimulated cells (p=0,014).Besides, neither Mtb-Ag nor PGE2 treatment modulated PD-L2 expression on human neutrophils. Moreover, we observed that PGE2 did not modify ROS production in Mtb-Ag stimulated neutrophils. Furthermore, significant higher levels of autophagy were detected in Mtb-Ag stimulated neutrophils from HD as compared to TB patients (p=0,042) but PGE2 treatment did not modify these levels. Taken together, our findings indicate that PGE2 treatment could alter PD-L1 surface expresssion on HD´s neutrophils, but had no effect on the levels of autophagy induced by Mtb-Ag, at least in our experimental conditions. Therefore, further experiments are required to determine the precise role of PGE2 on human neutrophils during active tuberculosis.