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

作者:Garcia Alvaro Baeza; Siu Edwin; Sun Tiffany; Exler Valerie; Brito Luis; Hekele Armin; Otten Gib; Augustijn Kevin; Janse Chris J; Ulmer Jeffrey B; Bernhagen Juergen; Fikrig Erol; Geall Andrew; Bucala Richard*
来源:Nature Communications, 2018, 9(1): 2714.
DOI:10.1038/s41467-018-05041-7

摘要

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.

  • 出版日期2018-7-13