Defense mechanisms of IFN-γ and LPS-primed murine microglia against Acanthamoeba castellanii infection

Abstract In the central nervous system (CNS), cytokine-primed microglia play a central role in host's defense against Acanthamoeba castellanii infection. In this study, the effect of recombinant interferon (rIFN)-γ and Salmonella enterica serovar enteritidis lipopolysaccharide (LPS), both inflammatory stimuli, on A. castellanii infection in murine microglia was examined. Priming of microglia with rIFN-γ and LPS synergistically triggered, in a dose-dependent manner, amebastatic activity in these cells. More than 52%, 88% or 95% of this function was then abrogated by anti-IL-1β (but not anti-IL-1α), IL-6 or TNF-α neutralizing antibodies, suggesting that these endogenously produced cytokines may participate in the antimicrobial capacity. Consistent with these findings, the priming of microglia with rIFN-γ and LPS elicited the release of proinflammatory interleukin (IL)-1α, IL-1β, IL-6 and tumor necrosis factor (TNF)-α. Since l -canavanine affected amebastatic activity only during the priming process but not during the infection process, NO-dependent pathway appears to be not the sole antiparasitic mechanism involved in this function. These data suggest that rIFN-γ and LPS, likely through a proinflammatory network, up-regulate the release of IL-β, IL-6 and TNF-α, which could trigger antimicrobial activity against A. castellanii infection in the brain.