Disabling the Camouflage Mechanism Used by Malaria Parasites

18/01/2013

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Gabriele Pradel

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In 2010, there were about 216 million malaria cases, and an estimated 700,000 malaria deaths. So far, there is no effective vaccine against the disease, and resistance to treatments is increasing. According to the World Health Organization (WHO), malaria remains one of the  greatest challenges in medicine today. A research group headed by PD Dr. Gabriele Pradel from the RWTH Institute for Molecular Biotechnology and involving scientists from universities in Jena, Würzburg, and Nijmegen has now published an article on the transmission of malaria in the scientific journal Cell Host and Microbe, titled “Malaria Parasites Co-opt Human Factor H to Prevent Complement-mediated Lysis in the Mosquito Midgut.” The article describes the mechanism used by the pathogen to prevent destruction by the human complement system.

 

As Pradel explains, "the spreading mechanism of the malaria pathogen is achieved in two steps. First, an Anopheles mosquito bites the human host, and the parasites take up residence in red blood cells, where they are protected from the human complement system. This system recognizes alien cells, such as micro-organisms, and destroys them. The human body’s own cells protect themselves against this mechanism by binding the factor H to their cell surface.

In order to spread the disease, the parasites need to reproduce. The sexual stage begins with the development of sexual precursor cells, the gametocytes, in the human body. Through subsequent mosquito bites, the gametocytes enter the mosquito’s gut, where within minutes, they develop into male and female gametes. Within one hour, the gametes fertilize to produce infectious cells capable of moving spontaneously, so-called ookinetes. The ookinetes further develop within the mosquito before they are transferred back to the body of a human host, again through a mosquito bite.

The sexual stage can be considered a “bottleneck” in the life cycle of a parasite: in order to be able to reproduce, the parasites have to leave the human blood cells and survive within the mosquito gut for about a day. The research team headed by Dr. Pradel found that the malaria pathogen binds factor H to its surface, thus assuming a camouflage that prevents destruction by the complement system, which is taken up by the mosquito with the blood meal and poses a threat to the parasites. The receptor for the factor H has been identified: According to Pradel, “intriguingly, it is a protein that in another parasite life cycle contributes to the locomotion of the parasite, moving to the surface of the pathogen only after it has entered the gut of the mosquito."

By disabling this camouflage mechanism, e.g. by inhibiting factor H or blocking its receptor, it becomes possible for the complement system to recognize and destroy the parasite in the gut of the mosquito. As Pradel points out, “this could be an important step toward a transmission-blocking vaccine. This type of vaccine becomes active in the mosquito gut after the blood meal, preventing the spread of the parasite.”