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

Nature Communications
Alvaro Baeza GarciaRichard Bucala

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-α, IL-12, and IFN-γ 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.

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Citations

Mar 6, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Cyrielle FougerouxPeter Johannes Holst
Sep 25, 2019·Vaccines·Leroy VersteegJeroen Pollet
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Nov 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Alvaro Baeza GarciaRichard Bucala

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Methods Mentioned

BETA
ELISA
flow cytometry
Tem
PCR
Fluorescence
electrophoresis

Software Mentioned

Prism
Spot Advanced
FlowJo
GraphPad
ImageJ
TreeStar

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