Abstract
Plasmodium sporozoites inoculated by Anopheles 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 was found to be detrimental for the parasite growth, leading to the acquisition of a long-lasting immune protection. Considering 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 P.berghei parasites that express murine IL-6 during liver stage development. Though IL-6 transgenic sporozoites develop into exo-erythrocytic forms in cultured hepatocytes in vitro, these parasites were not capable of inducing a blood stage infection in mice. Furthermore, immunization of mice with transgenic IL-6 sporozoites elicited a long-lasting CD8+ T cell-mediated protective immunity against a subsequent infectious sporozoite challenge. Collectively, this study demonstrates that parasite-encoded IL-6 impairs Plasmodium infection at the liver stage, forming the basis of a novel suicide vaccine strategy to elicit protective antimalarial immunity.
Competing Interest Statement
The authors have declared no competing interest.
Abbreviations
- ECM
- experimental cerebral malaria
- EEF
- exo-erythrocytic form
- GAP
- genetically-attenuated parasite
- Pb
- Plasmodium berghei
- SPZ
- sporozoite
- WT
- wild-type
