Une famille d'enzymes présentes des protozoaires aux mammifères: comment les phospholipases A 2 participent au processus d'invasion de Toxoplasma gondii

Abstract

Toxoplasma gondii is an intracellular obligate protozoan parasite. Human infection is generally subclinical but hosts with defective cellular immunity are at risk of severe disease. In many countries, congenital toxoplasmosis and toxoplasmic encephalitis in HIV-infected individuals are significant causes of morbidity and mortality. We review here the role of the members of phospholipases A 2 (PLA 2) family and how they participate in the invasion process of T. gondii. PLA 2 have been described in mammals cells as a family composed of nine groups of enzymes that specifically hydrolyse sn-2 bonds of phospholipids. Each PLA 2 group have a distinctive substrate preference, localization and way of activation indicating different physiological roles. We describe the existence of three PLA 2 isoforms in T. gondii. Inhibitors of secretory PLA 2 isoforms (sPLA 2) and cytosolic PLA 2 (cPLA 2), showed that cell and parasite sPLA 2 and parasite cPLA 2, but not cell cPLA 2, favours T. gondii invasion. The addition of IFNγ to cultured infected THP1 cells protected against T. gondii infection by an early mechanism involving a reduction in the number of parasitized cells. The reduction in the percentage of parasitized cells obtained by treatment with IFN γ is linked with a decrease in parasite and cellular PLA 2 activity. This is a new effector mechanism of IFN γ against T. gondii infection. The inhibitors of sPLA 2 type II have a pharmacological potential against T. gondii infection that remain to be tested in vivo.