Joseph Clark

"Engineered decoy-resistant IL-18 enhances innate and adaptive responses to Toxoplasma gondii but results in CD4 T cell dependent immune pathology"

Joseph Clark, Daniel Aldridge, Lindsey Shallberg, Jodi Gullicksrud, Ting Zhou, Aaron Ring and Christopher Hunter

IL-18 is an IL-1 family cytokine that amplifies NK and T cell IFN-g production, but In vivo its activity is limited by the IL-18 binding protein (IL18bp). The development of a variant IL-18 that is resistant to IL18bp (decoy-resistant IL-18, DR18), has been used to augment anti-tumor responses. In mice, infection with T. gondii induces high levels of IL18bp, and treatment with IL-18 had limited protective effects. However, treatment with DR18 was highly effected and promoted parasite control. Additionally, in infected mice DR18 treatment resulted in CD4+ T-cell-mediated immune pathology. This study highlights the importance of IL18bp in prevention of infection-induced pathology and informs efforts to utilize engineered IL-18 for immune therapy.