Neutralization of the Plasmodium-encoded MIF ortholog confers protective immunity against malaria infection.
Nat Commun
; 9(1): 2714, 2018 07 13.
Article
em En
| MEDLINE
| ID: mdl-30006528
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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Base de dados:
MEDLINE
Assunto principal:
Anticorpos Antiprotozoários
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Proteínas de Protozoários
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Fatores Inibidores da Migração de Macrófagos
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Vacinas Antimaláricas
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Vacinas de DNA
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Imunidade Adaptativa
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Malária
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article