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

Nana K. Minkah, Brandon K. Wilder, Amina A. Sheikh, Thomas Martinson, Lisa Wegmair, Ashley M. Vaughan and Stefan H. I. Kappe ()
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Nana K. Minkah: Seattle Children’s Research Institute
Brandon K. Wilder: Seattle Children’s Research Institute
Amina A. Sheikh: Seattle Children’s Research Institute
Thomas Martinson: Seattle Children’s Research Institute
Lisa Wegmair: Seattle Children’s Research Institute
Ashley M. Vaughan: Seattle Children’s Research Institute
Stefan H. I. Kappe: Seattle Children’s Research Institute

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: 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.

Date: 2019
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DOI: 10.1038/s41467-019-11819-0

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