Innate immunity limits protective adaptive immune responses against pre-erythrocytic malaria parasites

Nat Commun. 2019 Sep 2;10(1):3950. doi: 10.1038/s41467-019-11819-0.

Abstract

Immunization with attenuated whole Plasmodium sporozoites constitutes a promising vaccination strategy. Compared to replication-deficient parasites, immunization with replication-competent parasites confers better protection and also induces a type I IFN (IFN-1) response, but whether this IFN-1 response has beneficial or adverse effects on vaccine-induced adaptive immunity is not known. Here, we show that IFN-1 signaling-deficient mice immunized with replication-competent sporozoites exhibit superior protection against infection. This correlates with superior CD8 T cell memory including reduced expression of the exhaustion markers PD-1 and LAG-3 on these cells and increased numbers of memory CD8 T cells in the liver. Moreover, the adoptive transfer of memory CD8 T cells from the livers of previously immunized IFN-1 signaling-deficient mice confers greater protection against liver stage parasites. However, the detrimental role of IFN-1 signaling is not CD8 T cell intrinsic. Together, our data demonstrate that liver stage-engendered IFN-1 signaling impairs hepatic CD8 T cell memory via a CD8 T cell-extrinsic mechanism.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adaptive Immunity / immunology*
  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • CD8-Positive T-Lymphocytes / parasitology
  • Erythrocytes / immunology*
  • Erythrocytes / parasitology
  • Female
  • Immunity, Innate / immunology*
  • Immunization
  • Interferon Type I / immunology
  • Interferon Type I / metabolism
  • Liver / immunology
  • Liver / metabolism
  • Liver / parasitology
  • Malaria / immunology*
  • Malaria / parasitology
  • Malaria / prevention & control
  • Malaria Vaccines / administration & dosage
  • Malaria Vaccines / immunology
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Plasmodium yoelii / immunology*
  • Plasmodium yoelii / physiology
  • Sporozoites / immunology*
  • Vaccines, Attenuated / administration & dosage
  • Vaccines, Attenuated / immunology

Substances

  • Interferon Type I
  • Malaria Vaccines
  • Vaccines, Attenuated