Major disease-vector mosquito reveals the secrets of its immune system

The Culex quinquefasciatus mosquito poses a significant threat to human health as a blood-sucking transmitter of elephantiasis-causing worms and encephalitis-inducing viruses. An international team of scientists, including researchers from the University of Geneva and the SIB Swiss Institute of Bioinformatics sequenced its genome and studied its responses to pathogen infections. Two articles published in today's issue of Science, describe results from comparing the Culex mosquito with the malaria mosquito, Anopheles gambiae, and the dengue mosquito, Aedes aegypti, which offer new insights into the elimination of insect-transmitted diseases that seriously impact on global public health.

Mosquitoes are the most important disease-vectors. Species of CulexAedes, and Anopheles mosquitoes are responsible for the transmission of many human pathogens including parasites that cause malaria, viruses that trigger dengue and yellow fever, and West Nile encephalitis, as well as worms that cause lymphatic filariasis (also called elephantiasis). The capacity of different mosquito species to transmit these and other pathogens varies greatly, and much of this variation can be attributed to the mosquito immune system's ability to recognise and eliminate the pathogen. Applying their expertise in comparative evolutionary genomic analyses and insect immunity, Professor Evgeny Zdobnov and Dr Robert Waterhouse, from the University of Geneva Medical School and the SIB Swiss Institute of Bioinformatics, joined forces with scientists from around the world to examine the Culex genome and its encoded genes.

Sequencing of the Culex genome, directed by Peter Atkinson and Peter Arensburger from the University of California Riverside, allowed researchers to perform a thorough comparison among the three disease-vector mosquito species. Focusing on the mosquito immune system, researchers led by Professor Marc Muskavitch from Boston College, the Broad Institute, and Harvard School of Public Health, examined the responses of each mosquito species to different pathogens including parasites, viruses, bacteria, and worms, to identify genes that play a role in mosquito immune defences."Our pathogenomics study took advantage of the sequencing of the Culex quinquefasciatus genome" says Professor Muskavitch, "to bring together data from experiments profiling responses of mosquito genes to pathogen infections, directed by Professor Lyric Bartholomay, with the results of comparative immunogenomics analyses led by Dr Robert Waterhouse". This study revealed many differences among these three mosquito species, and also that Culex, the most geographically widespread, "has an expanded immune gene repertoire, which may enhance its ability to adapt to diverse habitats with different pathogen challenges", explains Dr Waterhouse.

"These important studies" says Professor Zdobnov, "highlight how genome sequencing can greatly facilitate detailed experimental investigations to uncover the complex biology of these major disease-vector mosquitoes". Professor Bartholomay, from Iowa State University, adds that "by comparing numerous combinations of mosquito species infected with different pathogen types, our results indicate that pathogens that successfully develop in, and are transmitted by, disease-vector mosquitoes, have evolved to avoid mosquito immune responses". Improving our understanding of these vector-pathogen relationships significantly advances the long-term objectives of developing strategies to reinforce the mosquitoes' defences, making them immune to infections and breaking the chain of pathogen transmission.