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. Recent studies using the P. chabaudi (Pch) mouse model to understand the reason for chronic malaria have shown that the programmed death-1 (PD-1) pathway inhibits T cell immunity against chronic blood-stage malaria. To determine if the PD-1 pathway inhibits long-term immunity, we infected wild type (WT) and PD-1KO mice with Pch malaria and measured protection as well as long-term immunity 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.
|Authors||Horne-Debets, Joshua M.; Karunarathne, Deshapriya S.; Faleiro, Rebecca J.; Poh, Chek Meng; Renia, Laurent; Wykes, Michelle N.|