1 University of Liverpool, UK
DiscussionApproximately 1-2 billion people are infected with T. gondii globally, making it one of the most successful protozoan parasites. With this in mind, we believe it is critical to better understand immunogenic ligands that may increase the pathogenicity of T. gondii during mammalian infections. Previous research on Systemic Lupus Erythematosus (SLE) demonstrated that cl-CD95L aggravates inflammation. Therefore, this study will delve into the role of cl-CD95L as an aggravating factor in the development of pathogenic T. gondii responses. To carry out this investigation VERO cells were used to deliver preliminary results on the impact cl-CD95L has on cell viability and cytotoxicity. Following on from this, bone-marrow derived macrophages (BMDM) were stimulated with cl-CD95L and infected with T. gondii. BMDM cultures were analysed to uncover through which pathways cl-CD95L may lead to an increase in parasitemia during infection. Finally, a Phospho-Kinase Array was utilized and determined that cl-CD95L amplifies protein expression in non-infected BMDM. Interestingly, the proteins expressed are similar to those of a myeloid-derived suppressor cell (MDSC). From the data collected we believe that cl-CD95L causes an MDSC like phenotype in previously un-polarized BMDM. The hallmark of MDSC activity is the increase in Arginase-1 expression which leads to the depletion of L-arginine, this in turn decreases the immune response against T. gondii, leading to an increase in parasite replication.