Interferon-gamma signal transduction during parasite infection: modulationof MAP kinases in the infection of human monocyte cells (THP1) by Toxoplasma gondii

We assayed mitogen-activated protein (MAP) kinase phosphorylation in a huma n monocyte cell line (THP1) during their infection by Toxoplasma gondii. In addition, we tested the effect of specific MAP kinase inhibitors (PD098059 and SB203580) on parasite invasion. MAP kinase phosphorylation was increas ed in the cytosol and membrane fractions of THP1 infected with T. gondii. T he MAP kinase phosphorylation of uninfected THP1 cells was not significantl y modified by incubation for 20 h with 1000 U/ml of IFN-gamma. However, IFN -gamma treatment of infected cells significantly reduces the increase in ph osphorylation. caused by parasite infection, There was also MAP kinase acti vity in the cytosol and membrane fractions of extracellular T. gondii tachy zoites. IFN-gamma altered the distribution of activity in subcellular fract ions of extracellular T. gondii tachyzoites. This indicates that IFN-gamma directly affects parasite MAP kinase activity. The results provide evidence that MAP kinase pathways participate in the infection by T. gondii and tha t the decrease in MAP kinase activity in infected cells caused by IFN-gamma may be involved in mediating their protective signals.