Plasmodium -encoded murine IL-6 impairs liver stage infection and elicits long-lasting sterilizing immunity

sporozoites (SPZ) inoculated by mosquitoes into the skin of the mammalian host migrate to the liver before infecting hepatocytes. Previous work demonstrated that early production of IL-6 in the liver is detrimental for the parasite growth, contributing to the acquisition of a long-lasting immune protection after immunization with live attenuated parasites. Considering that IL-6 as a critical pro-inflammatory signal, we explored a novel approach whereby the parasite itself encodes for the murine IL-6 gene. We generated transgenic parasites that express murine IL-6 during liver stage development. Though IL-6 transgenic SPZ developed into exo-erythrocytic forms in hepatocytes and , these parasites were not capable of inducing a blood stage infection in mice. Furthermore, immunization of mice with transgenic IL-6-expressing SPZ elicited a long-lasting CD8 T cell-mediated protective immunity against a subsequent infectious SPZ challenge. Collectively, this study demonstrates that parasite-encoded IL-6 attenuates parasite virulence with abortive liver stage of infection, forming the basis of a novel suicide vaccine strategy to elicit protective antimalarial immunity.