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

Front Immunol. 2023 Apr 11:14:1143012. doi: 10.3389/fimmu.2023.1143012. eCollection 2023.


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.

Keywords: CD8 T cells; IL-6; inflammation; liver; malaria; vaccine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes
  • Interleukin-6
  • Liver Diseases*
  • Malaria Vaccines*
  • Mammals
  • Mice
  • Plasmodium berghei


  • Interleukin-6
  • Malaria Vaccines
  • interleukin-6, mouse

Grants and funding

This work has been supported by the French Parasitology consortium ParaFrap (ANR-11-LABX0024), and by a grant from Institut Pasteur to SM.