Cell biology and immunology of malaria

Malaria is a vector-borne infectious disease caused by unicellular parasites of the genus Plasmodium. These obligate intracellular parasites have the unique capacity to infect and replicate within erythrocytes, which are terminally differentiated host cells that lack antigen presentation pathways. Prior to the cyclic erythrocytic infections that cause the characteristic clinical symptoms of malaria, the parasite undergoes an essential and clinically silent expansion phase in the liver. By infecting privileged host cells, employing programs of complex life stage conversions and expressing varying immunodominant antigens, Plasmodium parasites have evolved mechanisms to downmodulate protective immune responses against ongoing and even future infections. Consequently, anti-malaria immunity develops only gradually over many years of repeated and multiple infections in endemic areas. The identification of immune correlates of protection among the abundant non-protective host responses remains a research priority. Understanding the molecular and immunological mechanisms of the crosstalk between the parasite and the host is a prerequisite for the rational discovery and development of a safe, affordable, and protective anti-malaria vaccine.