Authors

M Mota¹;  ¹ Instituto de Medicina Molecular Liboa, Portugal

Discussion

Despite renewed eradication efforts from the international community, malaria still exerts an enormous disease burden, with nearly half the planet’s population at risk of infection. Within the human host, the disease-causing Plasmodium parasites pass through two distinct lifecycle stages, each in a different cellular environment. During the liver stage, a single Plasmodium sporozoite will invade a hepatocyte, and while sheltered there, supposedly undetected by the host, gives rise to thousands of new parasites, which will go on to initiate the subsequent blood stage of infection. While only 10-20 new parasites will be generated inside an erythrocyte, consecutive cycles of cell lysis and reinfection causing a potent host response, as well as the symptoms of malaria. The host contribution to infection outcome, on both the cellular and organismal levels has recently moved to center stage. We have identified hepatocyte molecules that modulate the success of liver stage infection, and showed that distinct host factors, not just the parasite itself, drive the onset and severity of diverse malaria syndromes. Our ongoing work indicates that the web of host-Plasmodium interactions is densely woven, with liver stage-mediated innate immune system activation, host nutritional status, and an antagonistic relationship between the two parasite stages themselves all working to modulate the balance between parasite replication and human health.