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

• Published in: Frontiers in immunology Vol. 14; p. 1143012
• Main Authors: Belhimeur, Selma, Briquet, Sylvie, Peronet, Roger, Pham, Jennifer, Commere, Pierre-Henri, Formaglio, Pauline, Amino, Rogerio, Scherf, Artur, Silvie, Olivier, Mecheri, Salaheddine
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers 11.04.2023; Frontiers Media S.A
• Subjects: Animals; CD8 T cells; CD8-Positive T-Lymphocytes; IL-6; Immunology; inflammation; Interleukin-6; Life Sciences; liver; Liver Diseases; malaria; Malaria Vaccines; Mammals; Mice; Plasmodium berghei; vaccine; vaccine; malaria; inflammation; liver; IL-6; CD8 T cells
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2023.1143012

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.