Malaria is one of three major infectious diseases affecting approximately 300 million people every year, accounting for about 500,000 deaths, but effective vaccine development has not been successful. Among malaria parasites infecting humans, Plasmodium falciparum (P. falciparum) causes especially severe disease.
In addition, acquired immunity to malaria is inefficient, even after repeated exposures to P. falciparum, but the immune regulatory mechanisms used by P. falciparum remain largely unclear. Therefore, malaria parasites appear to have a mechanism to escape our immune system.
A research group found that proteins called RIFIN expressed on erythrocytes infected with P. falciparum help the parasite to suppress the host immune response, causing severe malaria. RIFIN proteins are products of a polymorphic multigene family comprising approximately 150–200 genes per parasite genome that are expressed on the surface of infected erythrocytes.
Malaria parasites infect mainly erythrocytes in the host and proliferate within infected erythrocytes. The team found that proteins called RIFIN expressed on P falciparum-infected erythrocytes bind to either leucocyte immunoglobulin-like receptor B1 (LILRB1) or leucocyte-associated immunoglobulin-like receptor 1 (LAIR1). LILRB1-binding RIFINs inhibit activation of LILRB1-expressing B cells and natural killer (NK) cells. Furthermore, P. falciparum-infected erythrocytes isolated from patients with severe malaria were more likely to interact with LILRB1 than erythrocytes from patients with non-severe malaria.
This research disclosed for the first time in the world that P. falciparum has a new mechanism to suppress the host immune response by using an inhibitory receptor, contributing to the pathogenesis of severe malaria. The results of this research are expected to greatly contribute to the development of therapeutic drug and vaccine against malaria.
http://resou.osaka-u.ac.jp/en/research/2017/20171130_1
https://www.nature.com/articles/nature24994
Mechanism of immune evasion by malaria parasite unraveled!
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