Effects of cytokines and prolactin on the replication of Toxoplasma gondii in murine microglia.
In the central nervous system, cytokine-activated microglia play a crucial role in host defence against Toxoplasma gondii infections. In this study, the effect of recombinant tumor necrosis factor (rTNF)-alpha and prolactin (PRL) on T. gondii infection in microglia was examined. Pretreatment of microglia with rTNF-alpha and PRL induced toxoplasmastatic activity, the intracellular killing of T. gondii and the release of interleukin (IL)-1 beta IL-3 and IL-6: 50% of the intracellular killing was abrogated by anti-ICAM-1 monoclonal antibodies, whereas more than 54 or 87% of toxoplasmastatic activity was reversed by anti-IL-3 or IL-6 monoclonal antibodies. In addition, the treatment of microglia with either rIL-3 or rIL-6, in the absence or presence of rTNF-alpha significantly limited T. gondii replication. Inasmuch as either NMA or S-M-ITU affected cytokine-activated toxoplasmastatic activity during the infection phase, the NO-dependent pathway itself appears not to be directly involved in the parasitostatic activity. These findings suggest that TNF-alpha and PRL up-regulate the expression of ICAM-1 and the production of endogenous IL-6 and IL-3 by microglia, which could induce anti-parasitic functions against T. gondii infection in the brain.
Benedetto
N
N
Institute of Microbiology, Faculty of Medicine and Surgery, Second University of the Studies of Naples, Larghetto Sant'Aniello a Caponapoli 2, 80138 Naples, Italy.
Folgore
A
A
Romano Carratelli
C
C
Galdiero
F
F
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D007377:Interleukin-3 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D015850:Interleukin-6 / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D051379:Mice; D017628:Microglia / Q000378:metabolism / Q000469:parasitology*; D011388:Prolactin / Q000502:physiology*; D011994:Recombinant Proteins / Q000494:pharmacology; D014122:Toxoplasma / Q000254:growth & development*; D016781:Toxoplasmosis, Cerebral / Q000276:immunology / Q000469:parasitology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000911:Antibodies, Monoclonal; D007377:Interleukin-3; D015850:Interleukin-6; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D011388:Prolactin