Involvement of secretory and cytosolic phospholipases A2 during infection of THP1 human monocytic cells with Toxoplasma gondii. Effect of interferon γ

Abstract.

Toxoplasma gondii is an intracellular, obligate protozoan parasite that actively invades host cells. Phospholipases A2 (PLA2) are widely distributed enzymes that exist in many isoforms [secretory (sPLA2), cytosolic (cPLA2)] in monocytic and other human cells (pancreatic, kidney, etc) and also in parasites. We examined the effects of inhibitors of sPLA2 type II and cPLA2 on the invasion of human monocytic cells (THP1) by T. gondii (RH strain). We also measured sPLA2 type II and cPLA2 enzyme activities and their modulation by interferon γ (IFN γ) in extracts of host cells and parasite. Inhibition of both parasite and THP1 sPLA2 type II, and of parasite cPLA2 reduced the number of infected cells. Enzyme assays and immunoblot analyses demonstrated T. gondii sPLA2 type II and cPLA2 activities and indicated that T. gondii increased the activity of THP1 sPLA2 type II. Incubation with IFN γ (1,000 units/ml) for 20 h reduced the activities of sPLA2 and cPLA2 in infected and non-infected cells. Thus, IFN γ blocks the activities of both THP1 and parasite sPLA2 and cPLA2 in membrane fractions, resulting in protection against active invasion by T. gondii.