Wolbachia induces reactive oxygen species (ROS)-dependent activation of the Toll pathway to control dengue virus in the mosquito Aedes aegypti
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- 28 November 2011
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 109 (1), E23-31
- https://doi.org/10.1073/pnas.1116932108
Abstract
Wolbachia are maternally transmitted symbiotic bacteria that can spread within insect populations because of their unique ability to manipulate host reproduction. When introduced to nonnative mosquito hosts, Wolbachia induce resistance to a number of human pathogens, including dengue virus (DENV), Plasmodium, and filarial nematodes, but the molecular mechanism involved is unclear. In this study, we have deciphered how Wolbachia infection affects the Aedes aegypti host in inducing resistance to DENV. The microarray assay indicates that transcripts of genes with functions related to immunity and reduction-oxidation (redox) reactions are up-regulated in Ae. aegypti infected with Wolbachia. Infection with this bacterium leads to induction of oxidative stress and an increased level of reactive oxygen species in its mosquito host. Reactive oxygen species elevation is linked to the activation of the Toll pathway, which is essential in mediating the expression of antioxidants to counterbalance oxidative stress. This immune pathway also is responsible for activation of antimicrobial peptides-defensins and cecropins. We provide evidence that these antimicrobial peptides are involved in inhibition of DENV proliferation in Wolbachia-infected mosquitoes. Utilization of transgenic Ae. aegypti and the RNAi depletion approach has been instrumental in proving the role of defensins and cecropins in the resistance of Wolbachia-infected Ae. aegypti to DENV. These results indicate that a symbiotic bacterium can manipulate the host defense system to facilitate its own persistent infection, resulting in a compromise of the mosquito's ability to host human pathogens. Our discoveries will aid in the development of control strategies for mosquito-transmitted diseases.Keywords
This publication has 48 references indexed in Scilit:
- Wolbachia and the biological control of mosquito‐borne diseaseEMBO Reports, 2011
- Crosstalk of reactive oxygen species and NF-κB signalingCell Research, 2010
- RNA-based antiviral immunityNature Reviews Immunology, 2010
- The Toll immune signaling pathway control conserved anti-dengue defenses across diverse Ae. aegypti strains and against multiple dengue virus serotypesDevelopmental & Comparative Immunology, 2010
- Mosquito immune defenses against Plasmodium infectionDevelopmental & Comparative Immunology, 2010
- Innate antiviral immunity in DrosophilaCurrent Opinion in Immunology, 2010
- Antiviral immunity in drosophilaCurrent Opinion in Immunology, 2009
- DengueThe Lancet, 2007
- The Jak-STAT signaling pathway is required but not sufficient for the antiviral response of drosophilaNature Immunology, 2005
- GenMAPP, a new tool for viewing and analyzing microarray data on biological pathwaysNature Genetics, 2002