New types of mosquito immune cells, including a rare cell type that could be involved in limiting malaria infection, have been discovered by scientists creating the first cell atlas to map the insects’ immune cells.
Researchers from the Wellcome Sanger Institute, Umeå University, Sweden, and the National Institutes of Health (NIH), USA, who also identified molecular pathways implicated in controlling the malaria parasite, say the findings offer opportunities for uncovering novel ways to prevent mosquitoes from spreading the malaria parasite to humans and break the chain of malaria transmission.
In this first in-depth study of mosquito immune cells, the researchers studied Anopheles gambiae, which transmits malaria, and Aedes aegypti, which carries the viruses that causes Dengue, Chikungunya and Zika infections.
Using single cell techniques, the researchers analysed more than 8,500 individual immune cells to see which genes were switched on in each cell and to identify specific molecular markers for each unique cell type.
They found 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.
This enabled them to follow how Anopheles mosquitoes and their immune cells reacted to infection with the Plasmodium parasite.
First author Dr Gianmarco Raddi, from the Wellcome Sanger Institute, said: “We have carried out the first ever large-scale survey of the mosquito immune system, and using single cell sequencing technology we found immune cell types and cell states that had never been seen before.
“We also looked at mosquitoes that were infected with the Plasmodium parasite and for the first time were able to study their immune response in molecular detail, and identify which cells and pathways were involved.”
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.
This research discovered a rare, but important new cell type, which they named a Megacyte, which could be involved in immune priming, and which appears to switch on further immune responses to the Plasmodium parasite.
It is the first time a specific mosquito cell type has been implicated in regulating the control of malaria infection.
The researchers also showed that granulocytes increased in number in response to infection and revealed that some of these could develop into other immune cells. And 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.
Study author Dr Sarah Teichmann from the Wellcome Sanger Institute, said: “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.”
Raddi G and Barletta A et al. (2020) Mosquito cellular immunity at single-cell resolution. Science 27 August 2020.
https://science.sciencemag.org/lookup/doi/10.1126/science.abc0322
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