Fatty Acids Isolated from Toxoplasma gondii Reduce Glycosylphosphatidylinositol-Induced Tumor Necrosis Factor Alpha Production through Inhibition of the NF-κB Signaling Pathway

Abstract

Glycosylphosphatidylinositols (GPIs) are involved in the pathogenicity of protozoan parasites and are known to induce inflammatory cytokines. However, we have previously shown that the family of six GPIs of Toxoplasma gondii extracted together from tachyzoites could not induce tumor necrosis factor alpha (TNF-α) secretion by macrophages, whereas GPIs individually separated from this extract by thin-layer chromatography (TLC) were able to stimulate the cells. In the present study we show that the TLC step makes it possible to eliminate inhibitors extracted together with the T. gondii GPIs. Among the non-GPI molecules we have isolated fatty acids able to inhibit the secretion of TNF-α induced by the T. gondii GPIs. Myristic and palmitic acids reduce the production of TNF-α through the inhibition of tyrosine phosphorylation of cytoplasmic proteins and the inhibition of NF-κB activation in a peroxisome proliferator-activated receptor-independent pathway and after a rapid entry into the cytoplasm of macrophages. GPIs are considered toxins inducing irreversible damage in the host, and fatty acids produced in parallel by the parasite could reduce the immune response, thus favoring the persistence of parasite infection.