Defense mechanisms of IFN-gamma and LPS-primed murine microglia against Acanthamoeba castellanii infection.
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)-gamma and Salmonella enterica serovar enteritidis lipopolysaccharide (LPS), both inflammatory stimuli, on A. castellanii infection in murine microglia was examined. Priming of microglia with rIFN-gamma 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-1beta (but not anti-IL-1alpha), IL-6 or TNF-alpha neutralizing antibodies, suggesting that these endogenously produced cytokines may participate in the antimicrobial capacity. Consistent with these findings, the priming of microglia with rIFN-gamma and LPS elicited the release of proinflammatory interleukin (IL)-1alpha, IL-1beta, IL-6 and tumor necrosis factor (TNF)-alpha. 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-gamma and LPS, likely through a proinflammatory network, up-regulate the release of IL-beta, IL-6 and TNF-alpha, which could trigger antimicrobial activity against A. castellanii infection in the brain.
Benedetto
N
N
Section of Microbiology and Clinical Microbiology, Department of Experimental Medicine, Faculty of Medicine and Surgery, Second University of the Studies of Naples, Naples, Italy. nunzia.benedetto@unina2.it
Rossano
F
F
Gorga
F
F
Folgore
A
A
Rao
M
M
Romano Carratelli
C
C
D000048:Acanthamoeba / Q000187:drug effects*; D000562:Amebiasis / Q000188:drug therapy* / Q000276:immunology / Q000382:microbiology; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D002172:Canavanine / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000378:metabolism; D007202:Indicators and Reagents; D007371:Interferon-gamma / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D017628:Microglia / Q000187:drug effects*; D011994:Recombinant Proteins
D019138:Antibodies, Blocking; D016207:Cytokines; D007202:Indicators and Reagents; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D002172:Canavanine; D007371:Interferon-gamma