Poster Presentation First Malaria World Congress 2018

The complex role of programmed death-1 (PD-1) in preventing malarial immunity  (#400)

Michelle Wykes 1
  1. QIMR Berghofer, Brisbane, QLD, Australia

Plasmodium spp., exploit the programmed death-1 (PD-1)/PD-1 ligand-1 (PD-L1) pathway to 'deactivate' T cell functions. Such studies have led us to identify that higher PD-L2 expression on blood dendritic cells (DC), from Plasmodium falciparum-infected individuals, correlated with lower parasitemia. Mechanistic studies in mice showed that while PD-L1 expressed by DCs did indeed attenuate immune responses against malaria, PDL2 protein expressed on the same DCs improved immune responses by inhibiting PDL1–PD1 interactions. These studies also found that a multimeric form of PD-L2 (PDL2-Fc), given to mice infected with lethal malaria, was sufficient to mediate survival from the lethal infection compared to control mice (92% vs 0%) and mediate survival following re-infections after several months, without additional PDL2-Fc. Studies have now identified that PD-1 disarms a previously unknown arm of immunity which requires further investigation. Overall, these studies have established the importance of PD-1 mediated immuno-suppression and potential of targeting this pathway to be translated into an effective treatment for malaria.