Breanne Haskins  (Mentor: Christopher Hunter, PhD)

"CD8+ T cells provide protection during Cryptosporidium Infection"

Breanne Haskins, Jodi Gullicksrud, Jennifer Dumaine, Emma Hunter, Amandine Guérin, Bethan Wallbank, Ian Cohn, Keenan O’Dea, Ryan Pardy, Lindsey Rice, Jessica Byerly, Boris Striepen and Christopher Hunter

Cryptosporidium is an enteric pathogen that resides in an unusual intracellular, yet extracytoplasmic, subcellular location in intestinal epithelial cells. Due to the unique niche Cryptosporidium occupies, it is unknown how antigen is acquired by the immune system to activate a protective immune response, and it is unclear how T cells mediate resistance. For example, while T cell production of IFN is required for parasite control, there is also evidence of an IFN-independent, T cell-dependent mechanism of resistance. To study the T cell response to Cryptosporidium, we developed a novel model in which Cryptosporidium has been engineered to express SIINFEKL peptide. This allows us to use transgenic OT-I CD8+ T cells specific for SIINFEKL as a surrogate of Cryptosporidium-specific CD8+ T cells. In this model, I have already shown that these parasites induce a potent CD8+ T cell response, and that transfer of OT-I cells can promote control of Cryptosporidium. To determine how CD8+ T cells mediate protection, I infected IFN-Thy1.1 reporter mice with SIINFEKL-expressing parasites. Indeed, CD8+ T cells produce IFN during infection, and some were also specific to SIINFEKL antigen. This suggests that CD8+ T cell production of IFN is protective during infection. However, it is unknown how CD8+ T cells are primed to provide this protection. To determine if cDC1s, the dendritic cell (DC) subset classically thought to prime CD8+ T cells, were important during Cryptosporidium infection, IRF8+32-/- mice were infected and the CD8+ T cell response quantified. Mice that lacked cDC1s were more susceptible to infection and had decreased CD8+ T cell responses. These data suggest that cDC1s are critical for robust CD8+ T cell responses during Cryptosporidium infection. Together, my findings indicate that CD8+ T cells are protective during Cryptosporidium and this response requires DCs.