Why Mosquitoes Love Us

From that evil itch on your arm to torturous diseases such as malaria, Zika, dengue, and yellow fever, mosquito bites can have unpleasant consequences. But have you ever wondered why those skin-diving insects are so good at detecting humans? Not so surprisingly, the answer lies in neuroscience — in a special field called chemosensation, the sensing of chemical stimuli.

Chemosensation can be divided into two parts: the olfactory system responsible for smell, and the gustatory system responsible for taste. In each system, chemical compounds like odorants, food molecules, and pheromones bind to receptors, which initiate an electrical signal that travels to certain regions of the brain. However, smell and taste are not entirely independent of each other. Studies have shown that odor affects our taste perception (Stevenson et al., 1999). So the next time you want your lemon to taste less sour or your chocolate to taste sweeter, try smelling caramel while eating it.

The Basics of Chemosensation in Mosquitoes

Chemical communication plays an essential role in the lives of insects because it allows effective communication across long distances and a high-specificity perception of these signals. As with most insects, the main chemosensory organs in the mosquito are the antennae, the maxillary palps, and the labial palps. These tissues are covered in specialized sensory hairs called sensilla that typically contain two to three olfactory receptor neurons. The binding of a stimulant molecule, an odorant, initiates a cascade of protein interactions inside the olfactory receptor neuron that results in the generation of an action potential along its axon. Signals are then sent to the glomerulus, a structure that receives information from multiple receptors responsible for detecting similar odorant features. The activation pattern of the glomeruli cleverly encodes the chemical features of the odorant and is processed by the brain. As a result, the mosquito can detect particular plant volatiles, other mosquitoes’ pheromones, and lactic acid, a component of human odor. Interestingly, the binding of these odorant molecules is successful even when its source is not in the mosquito’s close proximity. In fact, mosquitoes can detect these chemical stimuli from 50 meters away, which suggests their heavy reliance on chemosensation for their daily operations such as foraging.

It’s not just chemistry, though

At the 2016 UCL Neuroscience Symposium, Dr. Leslie Vosshall at Rockfeller University presented a very intriguing study on understanding and modulating mosquito attraction to humans. She emphasized the importance of multimodal sensory integration — the synthesis of different cues such as moisture, odor, carbon dioxide, heat, and visual cues — for the ability of mosquitoes to detect humans.

When we breathe, we exhale carbon dioxide, and mosquitoes use this cue to find human hosts. In a recent study, Vosshall and her team mutated the AaegGr3 gene, which codes for a subunit of the carbon dioxide receptors, to render them inactive. When her team studied these mosquito’s host-seeking behavior, they found that not only could these mosquitoes not sense carbon dioxide, but other host-seeking senses were also disrupted, including heat! By imaging the glomerulus in mosquitoes using a two-photon microscope, they were able to observe this integration at the level of sensory neurons in the antennal lobes — structures involved in the olfactory system in insects that are strikingly similar to the olfactory bulb in humans. In other words, while each type of stimulus can have a small effect on its own, the combination of stimuli triggers significant behavioral responses.

Ever wonder why some people end up with more mosquito bites than their friends even when they’ve all been in the same place? The Vosshall Lab is studying the role of host physiology in mosquito attraction in an effort to identify the characteristics that make some of us more attractive to mosquitoes than others. It turns out that differences in skin odor alone can modulate mosquito attraction, even when other factors such as carbon dioxide and temperature are held constant. This is interesting because factors such as genetics, immunity, blood metabolites, diet, and [simple_tooltip content=’The collective genomes of skin microorganisms’]skin microbiome[/simple_tooltip], which all contribute to odor production, could be affecting the mosquito’s host preference.

A New Focus: Our Flavor

So we know that the integration of chemosensory stimuli lies behind a mosquito’s motivation to bite us. But how exactly does this work? Why are chemosensory systems in mosquitoes so adept at distinguishing humans from animals, and between different humans? These questions prompted researchers at Johns Hopkins University to examine which smells mosquitoes find delightful and which they find repulsive. And the results of these experiments turned out to be quite exciting and not at all what they expected.

A study conducted by Dr. Christopher Potter’s group suggested that a specialized area of the mosquito brain can mix taste with smell to create unique and preferred flavors. They designed membrane-targeted [simple_tooltip content=’A protein that glows bright green when exposed to particular wavelengths of light and used as a reporter to study cells.’]green fluorescent protein[/simple_tooltip] (GFP) to specifically label neuronal processes in olfactory receptor neurons of mosquitoes. They traced these GFP-labeled axons into the brain and found that they terminated in two main regions — one of which was expected and the other, startling! The projection of the olfactory receptor neurons from the antennae and maxillary palps to the antennal lobes was not surprising, as researchers knew that these structures play a significant role in olfaction. However, what they found really shocking was that olfactory receptor neurons from the labial palps projected to the subesophageal zone (SEZ), which had only ever been associated with taste! The finding came to be a significant discovery. This particular neuronal integration of the smell and taste may be the reason why mosquitoes love to suck our blood — because we taste good!

While previous research showed that the antennae and maxillary palps catch signals over long distances, this study now suggests that mosquitoes also use the labial palps in shorter distances to “smell” what the organism in front of them will “taste” like if they bite it. What does this mean for future designs of mosquito repellent? Dr. Potter says:

“This suggests that a combination of repellants could keep mosquitoes from biting us in two ways. One could target the antennal neurons and reduce the likelihood that they come too close, while another could target the labellar neurons and make the mosquitoes turn away in disgust — before sucking our blood — if they got close enough to land on us.”

The Future of Mosquito Research

Studying chemosensation in mosquitoes is a recent development in the field of neuroscience. Flies (Drosophila melanogaster) have been a common model in chemosensory research so far. However, these novel studies focused on host-seeking behavior in mosquitoes offer unique insights into creating preventive measures against many deadly mosquito-borne diseases.

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Written by Megumi Sano.

Images by Leslee Lazar.

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References:

Riabinina, O., Task, D., Marr, E., Lin, C. C., Alford, R., O’brochta, D. A., & Potter, C. J. (2016). Organization of olfactory centres in the malaria mosquito Anopheles gambiae. Nature communications, 7, 13010.

Stevenson, R. J., Prescott, J., & Boakes, R. A. (1999). Confusing tastes and smells: how odours can influence the perception of sweet and sour tastes. Chemical senses, 24(6), 627-635.

“Altering the ‘Flavor’ of Humans Could Help Fight Malaria.” October 10, 2016. Hopkins Medicine.