Hemocyte differentiation to the megacyte lineage enhances mosquito immunity against Plasmodium

  1. Ana Beatriz Ferreira Barletta
  2. Banhisikha Saha
  3. Nathanie Trisnadi
  4. Octavio Talyuli
  5. Gianmarco Raddi
  6. Carolina Barillas-Mury  Is a corresponding author
  1. National Institute of Allergy and Infectious Diseases, United States
  2. Atropos Therapeutics Inc, United States
  3. Universidade Federal Rural do Rio de Janeiro, Brazil
  4. University of Cambridge, United Kingdom

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

The following data sets were generated

Article and author information

Author details

  1. Ana Beatriz Ferreira Barletta

    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9913-3775
  2. Banhisikha Saha

    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, United States
    Competing interests
    No competing interests declared.
  3. Nathanie Trisnadi

    Atropos Therapeutics Inc, San Carlos, United States
    Competing interests
    Nathanie Trisnadi, is affiliated with Atropos Therapeutics Inc.. The author has no financial interests to declare.
  4. Octavio Talyuli

    Instituto de Bioquímica Médica Leopoldo de Meis, Universidade Federal Rural do Rio de Janeiro, Rio de Janeiro, Brazil
    Competing interests
    No competing interests declared.
  5. Gianmarco Raddi

    School of Clinical Medicine, University of Cambridge, Cambridge, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1056-5403
  6. Carolina Barillas-Mury

    Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, United States
    For correspondence
    cbarillas@niaid.nih.gov
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4039-6199

Funding

No external funding was received for this work

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.

Reviewing Editor

  1. Bruno Lemaitre, École Polytechnique Fédérale de Lausanne, Switzerland

Publication history

  1. Preprint posted: December 24, 2021 (view preprint)
  2. Received: June 16, 2022
  3. Accepted: September 1, 2022
  4. Accepted Manuscript published: September 2, 2022 (version 1)
  5. 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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  1. Ana Beatriz Ferreira Barletta
  2. Banhisikha Saha
  3. Nathanie Trisnadi
  4. Octavio Talyuli
  5. Gianmarco Raddi
  6. Carolina Barillas-Mury
(2022)
Hemocyte differentiation to the megacyte lineage enhances mosquito immunity against Plasmodium
eLife 11:e81116.
https://doi.org/10.7554/eLife.81116

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