Understanding the Role of Natural Killer Cells on the Quality of CD4 and CD8 Response During Infection with Toxoplasma gondii
thesisposted on 10.05.2017, 00:00 authored by Rida Fatima
30% of the world's population is infected by the obligate intracellular parasite Toxoplasma gondii including, more than 60 million people in the USA alone (CDC 2015). Toxoplasma poses a critical threat to individuals with a weakened immune system such as HIV/AIDS patients (Mayo Clinic 2014). In addition, severe birth defects, blindness, and abortion can occur in the fetus when the parasite is transmitted to healthy mothers who are pregnant (Sibley 2012). Thus, understanding how long term immunity develops against this parasite is important for better therapy design. Natural Killer cells (NK cells) are known to be important for early protection against Toxoplasma. Recently, in persistent viral infection NK cells have been shown to inhibit priming of CD4 and CD8 T cells during acute infection. We sought to understand whether this was happening during acute T. gondii infection. We tested whether NK cells impact the development of the protective T cell response. We observe the presence of NK cells helps boost early CD4 and CD8 T cell responses. Depletion of NK cells with a low or high dose of NK depleting antibody significantly reduced the T cell's ability to produce the cytokine IFNγ. Reduced T cell responses were also observed in NKT cell deficient animals. Our results indicate both NK and NKT cells are required for priming optimal T cell responses against the parasite and demonstrate the role of NK cells in parasite infection are different than their role in viral infection.