Activation of mosquito immunity blocks the development of transmission-stage filarial nematodes
Elizabeth B. Edgerton, Abigail Mccrea, Corbett T. Berry, Jenny Y. Kwok, Letitia Thompson, Brittany Watson, Elizabeth Mechem Fuller, Thomas J. Nolan, James B. Lok, Michael Povelones
Abstract
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.