3- Activation of the purinergic receptor P2Y6 is necessary to induce phagoptosis of neurons by microglia activated by B. abortus

ARIADNA FIORILLO; JULIA DE SANTIS AREVALO; JULIA RODRIGUEZ; GIAMBARTOLOMEI, GUILLERMO H; ANA M. RODRÍGUEZ

Mar del Plata

Congreso; Congreso Anual de SAIC-SAI-SAFIS-FAIC; 2022

SAI/SAIC/SAFIS

B. abortus-activated microglia kill neurons through primary phagocytosis or phagoptosis. Phagocytosis is a finely regulated process by the interaction of different receptors and their ligands. It has been shown that the purinergic pathway is involved in the modulation of different macrophages functions. The objective of this work was to investigate whether this signaling pathway is involved in the phagoptosis of neurons mediated by B. abortus-activated microglia. Primary cultures of neurons and microglia from Balb/c mice were infected. Neuron survival at 48 h was assessed by fluorescence microscopy. The cocultures were treated with apyrase enzyme (degrades di-tri nucleotides), RB2 (P2X/P2Y purinergic receptor inhibitor), BBG (P2X7 specific inhibitor) and MRS2578 (P2Y6 specific inhibitor). Treatment of B. abortus-infected cocultures with apyrase inhibited neuronal death, compared to untreated cultures (p0.05). By using the specific inhibitors of P2X7 and P2Y6, we were able to show that P2Y6, but not P2X7, is involved in the modulation of the phenomenon (p>0.05). In all cases, microglia activation was not affected, since there are no significant differences between treatments in TNF-α secretion (p>0.05). These results demonstrate that P2Y6 purinergic receptor and nucleotides would be necessary for neuronal death mediated by microglia activated by B. abortus, describing new molecular mechanisms involved in the pathogenesis of neurobrucellosis.