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Article Dans Une Revue Frontiers in Immunology Année : 2023

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

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Introduction: Plasmodium sporozoites (SPZ) 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 is detrimental for the parasite growth, contributing to the acquisition of a long-lasting immune protection after immunization with live attenuated parasites. Methods: 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 P. berghei parasites that express murine IL-6 during liver stage development. Results and Discussion: Though IL-6 transgenic SPZ developed into exo-erythrocytic forms in hepatocytes in vitro and in vivo, these parasites were not capable of inducing a blood stage infection in mice. Furthermore, immunization of mice with transgenic IL-6-expressing P. berghei 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 Plasmodium infection, forming the basis of a novel suicide vaccine strategy to elicit protective antimalarial immunity.
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pasteur-04144669 , version 1 (28-06-2023)

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Selma Belhimeur, Sylvie Briquet, Roger Peronet, Jennifer Pham, Pierre-Henri Commere, et al.. Plasmodium-encoded murine IL-6 impairs liver stage infection and elicits long-lasting sterilizing immunity. Frontiers in Immunology, 2023, 14, pp.1143012. ⟨10.3389/fimmu.2023.1143012⟩. ⟨pasteur-04144669⟩
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