Comparison of the GPIs of different mammalian stages of Trypanosoma cruzi

Chagas disease, caused by the protozoan Tryanosoma cruzi (T. cruzi), is a public health disease causing serious cardiac, gastrointestinal and neurological diseases. The vector for transmission of the parasite to the mammalian host is the triatomine bug which are mostly found in rural areas of Latin America, but globalization is at the origin of higher incidences in non-endemic countries. There is no vaccine and the treatment, which is essentially limited to nifurtimox and benznidazole, must be carried out for months and is responsible for severe side effects. Three different forms of T. cruzi have been identified in the vertebrate host: trypomastigotes, intracellular and extracellular amastigotes, the latter being the last described and the less analyzed. Glycosylphosphatidylinositols (GPIs) are protein membrane anchors present on the surface of all eukaryotic cells but in a much higher number on protozoans, also as protein-free molecules. GPIs are involved in the pathogenicity of diseases caused by protozoa by causing inflammatory reactions. The immunostimulatory and regulatory roles of trypomastigote GPIs on macrophages and TLR with consecutive cytokine production have already been proven, but nothing was known about the effect of amastigotes GPIs. The experiments conducted in the present work show different profiles of cytokine production, Toll-like receptors 2 and 4 activation, and major histocompatibility classes I and II expression after stimulation of macrophages, model kidney cells and dendritic cells, respectively, with the different GPIs of the three forms of T. cruzi. Taken the experiments together, it is obvious that the GPIs of amastigotes, the ones of the extracellular even more than the intracellular amastigotes, have a potent pro-inflammatory action, that is different from the one of trypomastigotes and in some cases even more potent. An analysis of the structure of the GPI side chains of the GPIs causing a higher immune reaction would certainly be helpful in order to understand the different reactions.