Molecules Identified Involved In Severe Malaria

Medical researchers at Osaka University have found that RIFIN proteins expressed on erythrocytes that were infected with Plasmodium falciparum help the parasite to suppress immune responses in the host, resulting in severe malaria. This research is expected to help in the further development of effective vaccines and in the development of therapeutic drugs against malaria.

There are three major infectious diseases: Tuberculosis, HIV/AIDS, and malaria. Approximately 300 million people are affected by it every year, with approximately 500,000 deaths from it.  Malaria is an infectious disease that is caused by malaria parasites. Development of an effective vaccine has yet to be discovered. The parasite plasmodium falciparum, the malaria parasite infecting humans, causes malaria to become the most severe. Acquired immunity has proven to be inefficient, even after repeated exposure to the parasite, the mechanisms used by the parasites still remain unclear. Meaning that the parasites associated with malaria would appear to have a mechanism to escape our immune system responses.

The research group from Osaka found RIFIN protein expressed on erythrocytes that were infected with the parasite plasmodium falciparum help the parasite to suppress the immune responses in the host leading to severe malaria. RIFIN proteins are encoded by the repetitive interspersed family genes of plasmodium falciparum in which there are about 150 rif genes per parasite genome, with the functions of unclear.

Erythrocytes in the host are infected by malaria parasites which then proliferate within the infectected erythrocytes. The team was able to identify that the proteins called RIFIN expressed on plasmodium falciparum infected erythrocytes bind to a host inhibitory receptor LILRB1. The immune system responses are suppressed by RIFIN, leading to severe complications of malaria. LILRB1 is one of the immune inhibitory receptors that suppresses the activation of immune cells and prevents autoimmune responses by recognizing self molecules such as MHC class. Human cytomegalovirus is known to contain a viral MHC class like molecule called UL18 which suppresses immune system responses via LILR81 for escape.

This new research has discovered and shown for the first time that plasmodium falciparum has a new mechanism to suppress the immune responses in the host by way of using an inhibitory receptor, resulting in the contributing to the pathogenesis of severe malaria. The findings of this research are expected to contribute towards the development of vaccines and therapeutic drugs against malaria.