AUTHOR=Belhimeur Selma , Briquet Sylvie , Peronet Roger , Pham Jennifer , Commere Pierre-Henri , Formaglio Pauline , Amino Rogerio , Scherf Artur , Silvie Olivier , Mecheri Salaheddine 

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

JOURNAL=Frontiers in Immunology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2023.1143012

DOI=10.3389/fimmu.2023.1143012

ISSN=1664-3224

ABSTRACT=<sec><title>Introduction</title><p><italic>Plasmodium</italic> sporozoites (SPZ) inoculated by <italic>Anopheles</italic> 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.</p></sec><sec><title>Methods</title><p>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 <italic>P. berghei</italic> parasites that express murine IL-6 during liver stage development.</p></sec><sec><title>Results and Discussion</title><p>Though IL-6 transgenic SPZ developed into exo-erythrocytic forms in hepatocytes <italic>in vitro</italic> and <italic>in vivo</italic>, these parasites were not capable of inducing a blood stage infection in mice. Furthermore, immunization of mice with transgenic IL-6-expressing <italic>P. berghei</italic> SPZ elicited a long-lasting CD8<sup>+</sup> 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 <italic>Plasmodium</italic> infection, forming the basis of a novel suicide vaccine strategy to elicit protective antimalarial immunity.</p></sec>