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The first mosquito cell atlas is published now in Science, where MIMS director, Oliver Billker, is one of the senior authors

MOSQUITO IMMUNE SYSTEM MAPPED TO HELP FIGHT MALARIA

Mosquito Thorax small 2Scientists have created the first cell atlas of mosquito immune cells, to understand how mosquitoes fight malaria and other infections. Researchers from the Wellcome Sanger Institute, Umeå University, Sweden and the National Institutes of Health (NIH), USA, discovered new types of mosquito immune cells, including a rare cell type that could be involved in limiting malaria infection. They also identified molecular pathways implicated in controlling the malaria parasite.

Published today (27 August, 2020) in Science, 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. The atlas will also be a valuable resource for researchers trying to understand and control other mosquito-borne diseases such as Dengue or Zika.
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.

Dr Gianmarco Raddi, a first author on the paper 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. 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.

Dr Oliver Billker, joint senior author on the paper previously from the Wellcome Sanger Institute and now based at Molecular Infection Medicine Sweden, Umeå University, said: “We discovered a rare but important new cell type we called a Megacyte, which could be involved in immune priming, and which appears to switch on further immune responses to the Plasmodium parasite. This is the first time a specific mosquito cell type has been implicated in regulating the control of malaria infection, and is a really exciting discovery. 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: “The team has created the first mosquito immune cell atlas, to shed light on how mosquito immune systems fight infections. 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.”


Contact details:
Dr Samantha Wynne, Media Officer
Wellcome Sanger Institute
Wellcome Genome Campus,
Hinxton, Cambridge, CB10 1SA, UK
Phone:+44 (0)1223 492368
Email: This email address is being protected from spambots. You need JavaScript enabled to view it.

Notes to editors:
*WHO malaria fact sheet: https://www.who.int/news-room/fact-sheets/detail/malaria
**Immune priming: Pre-exposure of Anopheles gambiae mosquitoes to Plasmodium infection, in the presence of the gut microbiota, enhances the ability of the mosquito immune system to respond to subsequent infections. This is a long-lasting response that means that mosquitoes who have previously been infected with Plasmodium are better able to control later Plasmodium infections. The immune priming response involves an increase in specific immune cells – the granulocytes. Understanding the mechanism could enable immunotherapy research to try to break the chain of transmission.


Publication:
Gianmarco Raddi and Ana Beatriz F. Barletta et al. (2020) Mosquito cellular immunity at single-cell resolution. Science. DOI 10.1126/science.abc0322

To read the full article, please go to: https://science.sciencemag.org/content/369/6507/1128.full

Funding:
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.

Selected websites:
Umeå University
Umeå University in the north of Sweden is one of the nation’s largest teaching universities with its over 34,000 students and 4,000 members of faculty and staff. We are characterised by strong research environments and a multitude of educations ranked highly in international comparison. Our campuses encourage cross-border meetings – between students, researchers, teachers and external parties alike. Through close collaborations with local and international stakeholders, we also contribute to making new and exciting things possible in society.
Molecular Infection Medicine Sweden
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. http://www.mims.umu.se

The Wellcome Sanger Institute
The Wellcome Sanger Institute is a world leading genomics research centre. We undertake large-scale research that forms the foundations of knowledge in biology and medicine. We are open and collaborative; our data, results, tools and technologies are shared across the globe to advance science. Our ambition is vast – we take on projects that are not possible anywhere else. We use the power of genome sequencing to understand and harness the information in DNA. Funded by Wellcome, we have the freedom and support to push the boundaries of genomics. Our findings are used to improve health and to understand life on Earth. Find out more at www.sanger.ac.uk or follow us on Twitter, Facebook, LinkedIn and on our Blog.

About Wellcome
Wellcome exists to improve health by helping great ideas to thrive. We support researchers, we take on big health challenges, we campaign for better science, and we help everyone get involved with science and health research. We are a politically and financially independent foundation. https://wellcome.ac.uk/

Image: Raddi et al. (2020) Science 369: 1128-1132, illustrating a mosquito thorax cross-esction under the microscope where the different colours indicate different cell types, labelled or stained by flurescent molecules and dyes. 

Battling antibiotic resistance

movie by Knut and Alice Wallenberg Foundation, with participation of scientists from MIMS and UCMR:
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https://kaw.wallenberg.org/

Research about infectious diseases:

Oliver Billker in movie of Knut and Alice Wallenberg Foundation:
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https://kaw.wallenberg.org/

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