Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection

Garcia, Alvaro Baeza; Siu, Edwin; Sun, Tiffany; Exler, Valerie; Brito, Luis; Hekele, Armin; Otten, Gib; Augustijn, Kevin; Janse, Chris J.; Ulmer, Jeffrey B.; Bernhagen, Jürgen; Fikrig, Erol; Geall, Andrew und Bucala, Richard (2018): Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection. In: Nature Communications, Vol. 9, 2714

Abstract

Plasmodium species produce an ortholog of the cytokine macrophage migration inhibitory factor, PMIF, which modulates the host inflammatory response to malaria. Using a novel RNA replicon-based vaccine, we show the impact of PMIF immunoneutralization on the host response and observed improved control of liver and blood-stage Plasmodium infection, and complete protection from re-infection. Vaccination against PMIF delayed blood-stage patency after sporozoite infection, reduced the expression of the Th1-associated inflammatory markers TNF-alpha, IL-12, and IFN-gamma during blood-stage infection, augmented Tfh cell and germinal center responses, increased anti-Plasmodium antibody titers, and enhanced the differentiation of antigen-experienced memory CD4 T cells and liver-resident CD8 T cells. Protection from re-infection was recapitulated by the adoptive transfer of CD8 or CD4 T cells from PMIF RNA immunized hosts. Parasite MIF inhibition may be a useful approach to promote immunity to Plasmodium and potentially other parasite genera that produce MIF orthologous proteins.

• Item Type: Journal article
• Faculties: Medicine
• Subjects: 600 Technology > 610 Medicine and health
• ISSN: 2041-1723
• Language: English