IL-6 SECRETED BY BRUCELLA ABORTUS-INFECTED ASTROCYTES INDUCES PHAGOCYTOSIS OF VIABLE NEURONS THROUGH BYSTANDER ACTIVATION OF MICROGLIA

JULIA RODRÍGUEZ; ANA MARÍA RODRÍGUEZ; GUILLERMO HERNÁN GIAMBARTOLOME

Buenos Aires

Congreso; Congreso Anual de SAI; 2021

SAI/SAIC

Central nervous system invasion by bacteria of the genus Brucella results in an inflammatory disorder called neurobrucellosis. We have previously demonstrated that soluble mediators released by B. abortus-infected astrocytes induces an inflammatory state in microglia and this bystander activation elicit neuronal death in primary neurons/microglia co-cultures. The aim of this work was to investigate the underlying mechanisms of this phenomenon. Primary cultures of murine astrocytes were infected or not with B. abortus for 24 h. After that, cell-free culture supernatants were used to stimulate primary co-cultures of murine neurons/microglia during 48 h. Neuronal density was evaluated by fluorescence microscopy. Blocking the phagocytic receptor vitronectin in microglia using cRGD peptide (an antagonist specific for this receptor) was sufficient to prevent neuronal loss (p0.05) in co-cultures treated with supernatants from infected astrocytes. Our previous results demonstrated that IL-6 secreted by B. abortus-infected astrocytes is at least one mediator involved in neuronal death through bystander activated-microglia. Neutralization of IL-6 in culture supernatants of infected astrocytes did not change microglial proliferation (assessed by microscopy; p>0.05) or microglial secretion of TNF-α (measured by ELISA; p>0.05), although did cause a reduced phagocytic activity of microglia (evaluated by phagocytosis assay with negatively charged fluorescent 5 μm beads; p