Mosquito Immune System Examined

Same Immune Factors Used to Fight Malaria Parasite and Infectious Pathogens

George Dimopoulos, PhD

Mosquitoes employ the same immune factors to fight off bacterial pathogens as they do to kill malaria-causing Plasmodium parasites, according to a study by researchers at the Johns Hopkins Bloomberg School of Public Health. The study identified several genes that encode proteins of the mosquito’s immune system. All of the immune genes that were involved in limiting infection by the malaria parasites were also important for the resistance to bacterial infection. However, several immune genes that were essential for resistance to bacterial infection did not affect Plasmodium infection. According to the authors, the findings add to the understanding of mosquito immunity, and could contribute towards the development of malaria-control strategies based on blocking the parasite in the mosquito. The study is published in the June 8, 2006, edition of PloS Pathogens.

“Mosquitoes that transmit malaria can kill large portions of Plasmodium parasites, and some mosquito strains are totally resistant to Plasmodium. However, our observations suggest that mosquitoes have not evolved a highly-specific defense against malaria parasites. Instead, they employ factors of their antimicrobial defense system to combat the Plasmodium parasite,” said George Dimopoulos, PhD, senior author of the study and assistant professor with the Bloomberg School’s Malaria Research Institute. “The degree of mosquito susceptibility to Plasmodium, and thereby its capacity to transmit malaria, may therefore partly depend on the mosquito’s microbial exposure, which can differ greatly between different geographic sites. Potentially, we could boost the mosquito’s capacity to fight the malaria parasite by exposing it to certain microbes or compounds that resemble the microbe molecules responsible for immune activation.”

In this study, the investigators also analyzed the immune responses of Anopheles gambiae mosquitoes to infection with different Plasmodium parasite species, one that causes malaria in humans and another that only infects rodents. The study revealed that mosquitoes mostly employ the same immune factors in defending against the two different Plasmodium species. Only a few immune genes were more important in the defense against either one of the two species.

“The mosquito’s immune system appears to employ a variety of antimicrobial defense factors (genes) against the malaria parasite, and can therefore significantly limit infection. The parasite, on the other hand, is capable of evading these defenses to a degree that allows its transmission by the mosquito. Now we have to figure out how to make the mosquito’s immune system more effective in killing malaria parasites at multiple stages that would render the development of evasive mechanisms impossible for the parasite,” said Dimopoulos.

Additional authors of the study include Yuemei Dong, Ruth Aguilar, Zhiyong Xi and Emma Warr of the W. Harry Feinstone Department of Molecular Microbiology and Immunology at the Johns Hopkins Bloomberg School of Public Health. Emmanuel Mongin is with the Department of Human Genetics and Genome at the Quebec Innovation Center at McGill University.

The research was supported by grants from the National Institute for Allergy and Infectious Diseases, the Ellison Medical Foundation, the World Health Organization Training in Tropical Diseases Program, Johns Hopkins Bloomberg School of Public Health and the Johns Hopkins Malaria Research Institute.