Prolactin-cytokine network in the defence against Acanthamoeba castellanii in murine microglia [corrected].
In the central nervous system, cytokine-primed microglia play a pivotal role in host defence against parasite infections. In this study, the effect of recombinant (r) prolactin (rPRL) and rIFN-gamma on A. castellanii infection in murine microglia was examined. Priming of microglia with rPRL and rIFN-gamma synergistically triggered, in a dose-dependent manner, amebastatic activity and the release of endogenous IL-1alpha, IL-1beta, IL-6 and TNF-alpha. More than 53, 57, 49, 89 or 96 % of amebastatic activity was abrogated by anti-PRLR, IFN-gammaR, IL-1beta (but not IL-1alpha), IL-6 or TNF-alpha antibodies, suggesting that these two receptors and proinflammatory cytokines participate in the anti-microbial function. Inasmuch as DPI and AET, both inhibitors of NO synthase, blocked amebastatic activity only during the priming process, the NO-dependent pathway itself appears not to be directly involved in the anti-parasitic capacity. These data suggest that the PRL/PRLR and IFN-gamma/IFN-gamma/R complexes, by the induction of the IFN-gammaR on microglia, up-regulate the release of endogenous TNF-alpha, IL-6 and IL-1beta by these cells, which could trigger anti-microbial activity against A. castellanii infection in the brain [corrected].
Benedetto
Nunzia
N
Institute of Microbiology, Faculty of Medicine and Surgery, Second University of the Studies of Naples, Italy. nunzia.benedetto@unina2.it
Auriault
Claude
C
D000048:Acanthamoeba / Q000254:growth & development / Q000472:pathogenicity*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D002478:Cells, Cultured; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004357:Drug Synergism; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000469:parasitology*; D009569:Nitric Oxide / Q000276:immunology; D011388:Prolactin / Q000008:administration & dosage / Q000494:pharmacology* / Q000502:physiology; D017471:Receptors, Interferon / Q000502:physiology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D000096743:Interferon gamma Receptor; D000093242:Interleukin-6 Inhibitors
D000911:Antibodies, Monoclonal; D016207:Cytokines; D007371:Interferon-gamma; D007375:Interleukin-1; D015850:Interleukin-6; D009569:Nitric Oxide; D011388:Prolactin; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D000096743:Interferon gamma Receptor; D000093242:Interleukin-6 Inhibitors