Open AccessMice lacking Programmed cell death-1 show a role for CD8+ T cells in long-term immunity against blood-stage malaria
Author(s) -
Joshua M. Horne-Debets,
Deshapriya S. Karunarathne,
Rebecca J. Faleiro,
Chek Meng Poh,
Laurent Rénia,
Michelle Wykes
Publication year - 2016
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/srep26210
Subject(s) - parasitemia , immunity , malaria , plasmodium chabaudi , immunology , cd8 , biology , acquired immune system , immune system , t cell , cytotoxic t cell , plasmodium falciparum , virology , genetics , in vitro
Even after years of experiencing malaria, caused by infection with Plasmodium species, individuals still have incomplete immunity and develop low-density parasitemia on re-infection. Previous studies using the P. chabaudi ( Pch ) mouse model to understand the reason for chronic malaria, found that mice with a deletion of programmed cell death-1 (PD-1KO) generate sterile immunity unlike wild type (WT) mice. Here we investigated if the mechanism underlying this defect during acute immunity also impacts on long-term immunity. We infected WT and PD-1KO mice with Pch -malaria and measured protection as well as immune responses against re-infections, 15 or 20 weeks after the original infection had cleared. WT mice showed approximately 1% parasitemia compared to sterile immunity in PD-1KO mice on re-infection. An examination of the mechanisms of immunity behind this long-term protection in PD-1KO mice showed a key role for parasite-specific CD8 + T cells even when CD4 + T cells and B cells responded to re-infection. These studies indicate that long-term CD8 + T cell-meditated protection requires consideration for future malaria vaccine design, as part of a multi-cell type response.