TY - JOUR
T1 - Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.
AU - Baeza Garcia, Alvaro
AU - Siu, Edwin
AU - Sun, Tiffany
AU - Exler, Valerie
AU - Brito, Lius
AU - Hekele, Armin
AU - Otten, Gib
AU - Augustijn, K.D.
AU - Janse, Chris
AU - Ulmer, Jeffrey
AU - Bernhagen, Jurgen
AU - Fikrig, Erol
AU - Geall, Andrew
AU - Bucala, Richard
PY - 2018/7/13
Y1 - 2018/7/13
N2 - 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.
AB - 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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U2 - 10.1038/s41467-018-05041-7
DO - 10.1038/s41467-018-05041-7
M3 - Article
SN - 2041-1723
VL - 9
JO - Nature Communications
JF - Nature Communications
IS - 2714
M1 - PMID: 30006528
ER -