Comparison of biological functions of glycosylphosphatidylinositols from a virulent and a non virulent strain of Toxoplasma gondii

• Applicant: Professor Dr. Ralph Thomas Schwarz
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens
• Term: from 2004 to 2010
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 5432008

Acute infection with Toxoplasma gondii results in the production of high levels of pro-inflammatory cytokines, such as IL-12 and TNFa. In turn, these cytokines initiate the production of IFN-g and various effector mechanisms that are responsible for the control of parasite growth and pathology during infection with T. gondii. However, little ist known about the mechanism by which T. gondii activates cells from innate immunity and initiates this early synthesis of pro-inflammatory cytokines. Toll-like receptors (TLRs) are the primary means the innate immune system has for recognizing and rapidly responding to the presence of microbes. To date, TLRs have been implicated in every known category of microorganisms that causes human diseases. Our recent study suggests that glycosylphosphatidylinositol (GPI) anchors from T. gondii tachyzoites have an important role in initiating the synthesis of TNFa by macrophages. We hypothesize that TLRs are central mediators in triggering signalling cascades that will lead to the synthesis of proinflammatory cytokines by cells from innate immunity exposed to GPI anchors derived from T. gondii. We propose to begin a careful evaluation of cells transfected with specific TLRs, in order to identify the TLR or TLRs activated by highly purified and synthetic GPI anchors derived from T. gondii. Sphingolipids of T. gondii seem to regulate the inflammmatory effects of the GPIs. Indeed, our preliminary results show that some of them inhibit the GPI-induced TNFa production. The aim of the next studies is to elucidate their structures and functions.

• DFG Programme: Research Grants