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

Selma Belhimeur1, Sylvie Briquet2, Roger Peronet1

  • 1Institut Pasteur, Université Paris Cité, CNRS ERL9195 and Inserm U1201, Unité de Biologie des Interactions Hôte Parasites, Paris, France.

Frontiers in Immunology
|May 5, 2023
PubMed
Abstract

Insights

Genetically engineered Plasmodium parasites expressing IL-6 were developed. These parasites failed to cause infection but generated long-lasting protective immunity, suggesting a novel malaria vaccine strategy.

Area of Science:

  • Malariology
  • Immunology
  • Parasitology

Background:

  • Plasmodium sporozoites (SPZ) migrate to the liver after mosquito inoculation.
  • Early liver-stage IL-6 production is detrimental to parasite growth and aids protective immunity.

Purpose of the Study:

  • To investigate the effect of parasite-encoded IL-6 on Plasmodium liver-stage development and host immunity.
  • To explore a novel vaccine strategy using genetically modified parasites.

Main Methods:

  • Generation of transgenic Plasmodium berghei parasites engineered to express murine IL-6 during the liver stage.
  • In vitro and in vivo assessment of parasite development and infectivity in mice.
  • Evaluation of immune responses and protective efficacy following immunization with IL-6-expressing SPZ.

Main Results:

  • IL-6 transgenic SPZ developed into exo-erythrocytic forms in hepatocytes but did not establish blood-stage infections.
  • Immunization with IL-6-expressing P. berghei SPZ induced robust, long-lasting CD8+ T cell-mediated protective immunity against subsequent SPZ challenge.
  • Parasite-encoded IL-6 attenuated parasite virulence, leading to abortive liver-stage infections.

Conclusions:

  • Parasite-encoded IL-6 acts as a virulence factor that aborts the Plasmodium liver stage.
  • This strategy forms the basis for a novel 'suicide vaccine' approach to elicit protective antimalarial immunity.
Keywords:
CD8 T cellsIL-6inflammationlivermalariavaccine

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