Mosquito immune system mapped to help fight malaria
Scientists from Umeå and the United States have created the first cell atlas of mosquito immune cells, to understand how mosquitoes fight malaria and other infections. They have discovered a rare cell type that could be involved in limiting malaria infection and identified molecular pathways involved in controlling the malaria parasite. The results have been published today in Science.
Text: Ingrid Söderbergh
Section through a mosquito head (to the left) and thorax (to the right), stained to help locate individual immune cells.
ImageGianmarco Raddi, Wellcome Sanger Institute
The study was conducted by scientists from Umeå University, the Wellcome Sanger Institute, and the National Institutes of Health (NIH), USA.
“Our results provide an opportunity to reveal new ways to break the chain of malaria transmission and prevent mosquitoes from spreading the malaria parasite to humans. “The atlas will also be a valuable resource for researchers trying to understand and control other mosquito-borne diseases such as Dengue or Zika,” says Oliver Billker, professor at the research center Molecular Infection Medicine Sweden (MIMS) at Umeå University, and joint senior author on the paper.
Malaria is a life-threatening disease that affects more than 200 million people worldwide and caused an estimated 405,000 deaths in 2018 alone, the majority of which were children under five. It is caused by Plasmodium parasites, which are spread via the bites of female Anopheles mosquitoes. Breaking the chain of transmission from human to mosquito to human is key for reducing the burden of malaria.
The mosquito immune system controls how the insect can tolerate or transmit parasites or viruses, however little is known about the exact cell types involved. In this first in-depth study of mosquito immune cells, a team of researchers studied two types of mosquito: Anopheles gambiae, which transmits malaria, and Aedes aegypti, which carries the viruses that causes Dengue, Chikungunya and Zika infections.
Using cutting edge single cell techniques, the researchers analysed more than 8,500 individual immune cells to see exactly which genes were switched on in each cell and identify specific molecular markers for each unique cell type. The team discovered there were at least twice as many types of immune cell than had previously been seen, and used the markers to find and quantify these cells in circulation, or on the gut and other parts of the mosquito. They were then able to follow how Anopheles mosquitoes and their immune cells reacted to infection with the Plasmodium parasite.
A previous study from the NIH team had shown that a process called immune priming could limit the ability of mosquitoes to transmit malaria, by activating the mosquito immune system to successfully fight the parasite.
In this study, the researchers discovered that one of the newly discovered immune cell types had high levels of a key molecule needed for immune priming, and could be involved in that process.
“This is the first time we can see that a specific cell type in mosquitoes is involved in regulating the control of malaria infection, and it is a really exciting discovery,” says Oliver Billker. “This rare but important new cell type, which we have named Megacyte, appears to switch on further immune responses against the Plasmodium parasite. We now need to carry out further studies to validate this and better understand these cells and their role.”
The researchers showed that specific types of immune cell – granulocytes – increased in number in response to infection, and revealed that some of these could develop into other immune cells. They also discovered that immune cells in the mosquito’s gut and other tissues are actively recruited into the circulation to fight infections after lying dormant on the mosquito fat body.
Dr Sarah Teichmann, an author from the Wellcome Sanger Institute, said: “Mosquitos appear to have a sweet spot of immunity to parasites like malaria, with enough immunity to the infection that it doesn’t kill the mosquito but not enough to remove the parasite. This atlas offers a vital resource for further research, which could reveal ways to modify the mosquito immune response to break the chain of disease transmission.”
This study was supported by the National Institute of Allergy and Infectious Diseases (NIAID), NIH, UCLA-Caltech, Wellcome, the Knut and Alice Wallenberg Foundation and the European Research Council.
Gianmarco Raddi, Ana Beatriz F. Barletta, Mirjana Efremova, Jose Luis Ramirez, Rafael Cantera, Sarah A. Teichmann, Carolina Barillas-Mury, Oliver Billker: Mosquito cellular immunity at single-cell resolution. Science (2020). DOI: 10.1126/science.abc0322
About the Molecular Infection Medicine Sweden (MIMS)
The Laboratory for Molecular Infection Medicine Sweden is based at Umeå University. It is the Swedish node of the Nordic EMBL Partnership for Molecular Medicine. We foster the next generation of scientists to conduct outstanding research into molecular microbiology and infection medicine.