One of the major public health issues of the developing world is the spread of malaria, a disease that afflicts about 500 million people and kills between one and three million people worldwide each year. Malaria is caused by the transmission of the Plasmodium parasite from the salivary glands of female Anopheles mosquitoes to human blood.
Since no vaccination currently exists for this disease and the parasite has become increasingly drug-resistant, a promising method of preventing the spread of malaria is to target its principal vector, the mosquito.
Improved knowledge of the workings of the Anopheles immune system hints at the possibility of creating genetically modified Plasmodium-resistant mosquitoes to stop the spread of malaria. It appears that a protein called GNBP is necessary for mosquitoes that harbor the Plasmodium parasite.
In order to study the role of GNBP in the mosquito immune system, researchers at the Department of Molecular Microbiology and Immunology of the Bloomberg School of Public Health have focused on the mosquito genome as the center of their investigation.
The immune system of the Anopheles mosquito is innately able to recognize Plasmodium as a foreign substance and responds in such ways to combat the parasite.
Cellular and humoral defense mechanisms in mosquito are triggered by pattern recognition receptor (PRR) molecules, which bind to pathogen-associated molecular patterns (PAMPs) on a pathogen such as a parasite. This is analagous to the way the human immune system uses antibodies to target invading pathogens.
These receptors are capable of inducing direct target-and-destroy mechanisms within the Anopheles immune system as well as triggering the activation of pathways that leads to the transcription of antimicrobial peptides.
An RNAi-based gene silencing approach was used for the main part of this study - investigating the role of GNBPs as defense mechanisms against Plasmodium in the Anopheles mosquito.
By shutting off expression of GNBPs in the mosquito immune system, then feeding them with Plasmodium-infected blood, the researchers were able to assess whether the gene was a necessary part of the mosquito's interactions with the parasite.
Results showed that GNBPB4 plays an important role in the defense against pathogens. Mosquitoes without functioning GNBPB4 had a much greater infection rate with parasites. Furthemore, microscopic investigations found that in normal mosquitoes the GNBPB4 antibody was targeted to Plasmodium eggs.
GNBPB4's interaction with Plasmodium is in sync with previous literature results, which indicated that the Anopheles immune system is active in defense against the parasite. Ultimately, our knowledge of how GNBPs work will aid in the development for novel methods of malaria control based on eliminating the parasite from the Anopheles mosquito vector population.
