Immunity to Toxoplasma gondii and the role of interleukin-27 and its subunits in the regulation of inflammation

T. gondii is a single-celled, protozoan parasite that causes disease in humans and other mammals. In addition to its clinical importance, T. gondii has also served as an important tool in the laboratory to study the immune system. In particular, the study of immunity to T. gondii has led to the discovery of numerous mechanisms of immune regulation. Examination of the host response to different T. gondii strains has highlighted the important role of host-pathogen interactions in shaping the immune response, and a toxoplasmosis model has been used to describe the anti-inflammatory properties of the cytokine interleukin (IL)-27. The studies presented in this thesis show that virulent and avirulent strains of T. gondii can differentially influence the murine immune response to determine the outcome of infection. Other studies described here examined cytokine-dependent processes during T. gondii infection and in response to various immunization strategies to reveal a role for the IL-27p28 subunit as a cytokine receptor antagonist. Finally, additional work showed that IL-27 can influence the homeostasis of T regulatory cells (T reg), a vital population of immune suppressors that prevent autoimmunity. Together, the body of work summarized here provides new insights into immune regulation during toxoplasmosis and in response to IL-27 and its subunits.