Hemocyte differentiation to the megacyte lineage enhances mosquito immunity against Plasmodium
Abstract
Activation of Toll signaling in Anopheles gambiae by silencing Cactus, a suppressor of this pathway, enhances local release of hemocyte-derived microvesicles (HdMv), promoting activation of the mosquito complement-like system, which eliminates Plasmodium ookinetes. We uncovered the mechanism of this immune enhancement. Cactus silencing triggers a Rel1-mediated differentiation of granulocytes to the megacyte lineage, a new subpopulation of giant cells, resulting in a dramatic increase in the proportion of circulating megacytes. Megacytes are very plastic cells that are massively recruited to the basal midgut surface in response to Plasmodium infection. We show that Toll signaling modulates hemocyte differentiation and that megacyte recruitment to the midgut greatly enhances mosquito immunity against Plasmodium.
Data availability
Sequencing data have been deposited in ArrayExpress under this linkhttps://www.ebi.ac.uk/biostudies/arrayexpress/studies/E-MTAB-11252
Article and author information
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Funding
No external funding was received for this work
Reviewing Editor
- Bruno Lemaitre, École Polytechnique Fédérale de Lausanne, Switzerland
Ethics
Animal experimentation: Public Health Service Animal Welfare Assurance #A4149-01 guidelines were followed according to the National Institutes of Health Animal (NIH) Office of Animal Care and Use (OACU). These studies were done according to the NIH animal study protocol (ASP) approved by the NIH Animal Care and User Committee (ACUC), with approval ID ASP-LMVR5.
Version history
- Preprint posted: December 24, 2021 (view preprint)
- Received: June 16, 2022
- Accepted: September 1, 2022
- Accepted Manuscript published: September 2, 2022 (version 1)
- Version of Record published: October 6, 2022 (version 2)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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