Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes

Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of Aede...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2020-02, Vol.117 (7), p.3711-3717
Main Authors: Edgerton, Elizabeth B., McCrea, Abigail R., Berry, Corbett T., Kwok, Jenny Y., Thompson, Letitia K., Watson, Brittany, Fuller, Elizabeth M., Nolan, Thomas J., Lok, James B., Povelones, Michael
Format: Article
Language:English
Subjects:
Activation
Aedes - genetics
Aedes - immunology
Aedes - parasitology
Aedes aegypti
Animals
Biological Sciences
Coronary artery disease
Developmental stages
Dirofilaria immitis - growth & development
Disease transmission
Filariasis
Genetic engineering
Heart diseases
Immune response
Immune system
Immunity
Infections
Insect Proteins - genetics
Insect Proteins - immunology
Larva - growth & development
Larvae
Larval development
Mosquito Vectors - genetics
Mosquito Vectors - immunology
Mosquito Vectors - parasitology
Mosquitoes
Nematodes
Parasites
Pathogens
Signal transduction
Vector-borne diseases
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Summary:Mosquito-borne helminth infections are responsible for a significant worldwide disease burden in both humans and animals. Accordingly, development of novel strategies to reduce disease transmission by targeting these pathogens in the vector are of paramount importance. We found that a strain of Aedes aegypti that is refractory to infection by Dirofilaria immitis, the agent of canine heartworm disease, mounts a stronger immune response during infection than does a susceptible strain. Moreover, activation of the Toll immune signaling pathway in the susceptible strain arrests larval development of the parasite, thereby decreasing the number of transmission-stage larvae. Notably, this strategy also blocks transmission-stage Brugia malayi, an agent of human lymphatic filariasis. Our data show that mosquito immunity can play a pivotal role in restricting filarial nematode development and suggest that genetically engineering mosquitoes with enhanced immunity will help reduce pathogen transmission.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1909369117