Download Innate immunity against malaria: studies on the mechanisms of Plasmodium -phagocyte interactions and their consequences.

NUS Graduate School for Integrative Sciences and Engineering
Research Project Write-up
Title of Project :
Innate immunity against malaria: studies on the
mechanisms of Plasmodium-phagocyte interactions and
their consequences
Name of Supervisor :
Dr. Kevin SW Tan
Contact Details:
[email protected]
Short Description
Malaria remains a major disease and cause of death in tropical countries. Confronted by the
increasing parasite resistance to current drugs, the development of a safe and effective vaccine
is essential. Thus, research on the immunology of malaria has mainly focused on adaptive
immunity. The potential for innate immune mechanisms to provide rapid protection against
malaria have largely been neglected. Recent studies from animal models, and clinical studies
have demonstrated that innate immune cells directed against Plasmodium infected red blood
cells contribute to protection from malaria and modulate adaptive immune responses. In the
blood, both monocytes and neutrophils are the first cells to interact with infected red blood
cells (iRBC) and tissue macrophages in the spleen and in the liver are crucial for parasite
clearance. In vitro studies have shown that these cell types can kill P. falciparum parasites
directly after phagocytosis or indirectly after cytokine release. However, the exact role of the
cells involved in the innate responses and the malarial ligands and host receptor involved in
the innate response are not completely elucidated.
The aim of this project is to identify the parasite ligands involved in iRBC adhesion and
phagocytosis by macrophages and neutrophils and their reciprocal ligands. We will use both
P. falciparum and P. vivax, the two most deadly parasites, in our studies. We will also
investigate the induction of gene expression in stimulated phagocytes and the reciprocal effect
on gene expression in the parasites. This knowledge will hep identify the innate immune
pathways induced by the parasites and their effects on the parasites.