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

• Published in: International immunopharmacology 2003-06, Vol.3 (6), p.825-834
• Main Authors: Benedetto, N., Rossano, F., Gorga, F., Folgore, A., Rao, M., Romano Carratelli, C.
• Format: Article
• Language: English
• Subjects: A. castellanii; Acanthamoeba - drug effects; Amebiasis - drug therapy; Amebiasis - immunology; Amebiasis - microbiology; Animal protozoal diseases; Animals; Antibodies, Blocking - pharmacology; Biological and medical sciences; Canavanine - pharmacology; Cell Division - drug effects; Cells, Cultured; Cytokine; Cytokines - antagonists & inhibitors; Cytokines - metabolism; Indicators and Reagents; Infectious diseases; Interferon-gamma - pharmacology; Lipopolysaccharides - pharmacology; LPS; Medical sciences; MGC; Mice; Mice, Inbred BALB C; Microglia - drug effects; Parasitic diseases; Protozoal diseases; Recombinant Proteins
• ISSN: 1567-5769; 1878-1705
• DOI: 10.1016/S1567-5769(03)00047-X

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.