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How mosquitoes distinguish people from animals

Scientists gained insights into how Aedes aegypti mosquitoes target humans over other animals. James Gathany, CDC

One form of Aedes aegypti mosquito has evolved to specialize in biting people, and is responsible for spreading many human pathogens, including the dengue, West Nile, and Zika viruses. These mosquitoes originated in Africa and are now found throughout the world.

Mosquitoes can sense the carbon dioxide that animals exhale. Yet, how mosquitoes specifically recognize people isn’t well understood. Female Aedes aegypti mosquitoes strongly prefer human odor over the odors of other animals, but how they make this distinction is unknown.

An NIH-funded research team at Princeton University set out to investigate how these mosquitoes distinguish human odors from those of other animals. The team was led by Dr. Zhilei Zhao, now at Cornell University, and Dr. Carolyn S. McBride. Results were published on May 4, 2022, in Nature.

Mosquitoes detect odor molecules using receptors in thousands of sensory neurons in their antennae, mouthparts, and maxillary palps (the structures between their antennae and mouthparts). Neurons triggered by the same odor receptors are thought to connect to the same areas in the antennal lobe of the mosquito brain. Each of these distinct areas is called a glomerulus.

The researchers used CRISPR-Cas9 gene-editing technology to create a system that allowed them to detect when specific glomeruli were activated by odors. They tested odors from people, rats, guinea pigs, quail, sheep wool, and dog hair. They also tested milkweed flowers and honey, which mosquitoes also find attractive.

Human and animal odors activated distinct combinations of glomeruli in the antennal lobe of the mosquito brain. One glomerulus was activated by both human and animal odors. Another responded strongly to animal odors but not to human odor. One responded strongly to human odor but not to the animal ones.

When the researchers analyzed the components of the different odors, they identified a uniquely human bouquet that could be distinguished by the combination of a small but diverse set of compounds. None of these compounds were found only in humans. The team tested the compounds in mosquitoes and pinpointed which ones activated the human-detecting glomerulus. Those that specifically activated this glomerulus were likely from sebum, the oily substance secreted at the base of hair follicles.

Finally, the team confirmed that mosquitoes were attracted to a synthetic mix the scientists made of the compounds that activated the human-detecting glomerulus.

“The simplicity surprised us,” McBride says. “Despite the complexity of human odor, and the fact that it doesn't really have any kind of human-specific compounds in it, the mosquitoes have evolved a surprisingly simple mechanism for recognizing us.”

These insights into how mosquitoes detect people may help researchers design more effective approaches to prevent mosquitoes from finding human hosts.