Toxo reduces GPI-induced TNF{alpha} production through inhibition of NF-{kappa}B pathway

Infect Immun. 2007 Mar 26; [Epub ahead of print]

Fatty acids isolated from Toxoplasma gondii reduce GPI-induced TNF{alpha} production through inhibition of NF-{kappa}B signaling pathway.

Debierre-Grockiego F, Rabi K, Schmidt J, Geyer H, Geyer R, Schwarz RT.

Institut fur Virologie, AG Parasitologie, Hans-Meerwein-Str. 2, D-35043 Marburg, Germany, and Institut fur Biochemie, Friedrichstrasse 24, D-35392 Giessen, Germany, and Unite de Glycobiologie Structurale et Fonctionnelle UMR CNRS/USTL n degrees 8576 - IFR 118, F-59655 Villeneuve D'Ascq, France.

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 TNF-alpha 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 permits 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-alpha induced by the T. gondii GPIs. Myristic and palmitic acids reduce the production of TNF-alpha through the inhibition of tyrosine phosphorylation of cytoplasmic proteins and the inhibition of NF-kappaB activation in a PPAR-independent pathway and after a rapid entry into the cytoplasm of macrophages. GPIs are considered as toxin inducing irreversible damages in the host, and fatty acids produced in parallel by the parasite could reduce the immune response thus favoring the persistence of parasite infection.

PMID: 17387164 [PubMed - as supplied by publisher]