Mosquito-borne diseases affect hundreds of millions of people every year, with a disproportionate impact on the developing world. One mosquito species, Aedes aegypti, is a primary vector of viruses that cause dengue, yellow fever, and Zika.

Male mosquitoes are harmless, but females need blood for egg development. Scientists have over many years of research discovered that there is no single cue that these insects rely on to locate a potential host for their next blood meal. Instead, the insects integrate multiple cues, such as CO2 from breath, skin odor, and visual cues, at different ranges.

A team led by researchers at the University of California, Santa Barbara (UCSB), has added infrared detection to the mosquito’s documented repertoire of senses. In a series of newly reported studies, the investigators found that infrared radiation (IR) from a source roughly the temperature of human skin doubled the insects’ overall host-seeking behavior when combined with CO2 and human odor. The mosquitoes overwhelmingly navigated toward this infrared source while host-seeking. The researchers also discovered where this infrared detector is located and how it works on a morphological and biochemical level.

The team’s discovery could provide a way to improve methods for suppressing mosquito populations. For instance, incorporating thermal IR from sources around skin temperature could make mosquito traps more effective. The findings also help explain why loose-fitting clothing is particularly good at preventing bites. Not only does it block the mosquito from reaching our skin, it also allows the IR to dissipate between our skin and the clothing so the mosquitoes cannot detect it.

“Despite their diminutive size, mosquitoes are responsible for more human deaths than any other animal,” said co-lead author Nicolas DeBeaubien, PhD, a former graduate student and postdoctoral researcher at UCSB, in the lab of research lead Craig Montell, PhD, the Duggan and Distinguished Professor of Molecular, Cellular, and Developmental Biology. “The mosquito we study, Aedes aegypti, is exceptionally skilled at finding human hosts. This work sheds new light on how they achieve this … Our research enhances the understanding of how mosquitoes target humans and offers new possibilities for controlling the transmission of mosquito-borne diseases.”

Loose fitting clothing lets through less IR. [DeBeaubien and Chandel et al.]
Loose-fitting clothing lets through less IR. [DeBeaubien and Chandel et al.]
Senior author Montell, DeBeaubbien, and colleagues, reported on their findings in Nature, in a paper titled “Thermal infrared directs host-seeking behavior in Aedes aegypti mosquitoes.” Commenting on their collective results, the team wrote, “The realization that thermal IR radiation is an outstanding mid-range directional cue expands our understanding as to how mosquitoes are exquisitely effective in locating hosts … the finding that thermal IR is an effective host-seeking cue raises the possibility of developing strategies to interfere with this attraction, and the opportunity to devise more effective mosquito baits.”

While a mosquito bite is often no more than a temporary bother, in many parts of the world it can be significant. One mosquito species, Ae. aegypti, spreads the viruses that cause over 100,000,000 cases of dengue, yellow fever, Zika, and other diseases every year. Another, Anopheles gambiae, spreads the parasite that causes malaria. World Health Organization estimates cited by the authors suggest that malaria alone causes more than 400,000 deaths every year. Their capacity to transmit disease has earned mosquitoes the title of deadliest animal.

Co-lead author Avinash Chandel, PhD, a current postdoc at UCSB in Montell’s group, suggested that half the world’s population is at risk for mosquito-borne diseases, and about a billion people get infected every year. Climate change and worldwide travel have extended the ranges of Ae. aegypti beyond tropical and subtropical countries. These mosquitoes are now present in places in the United States where they were never found just a few years ago, including California.

It is well established that mosquitoes like Ae. aegypti use multiple cues to home in on hosts from a distance. “These include CO2 from our exhaled breath, odors, vision, [convection] heat from our skin, and humidity from our bodies,” explained co-lead author Avinash Chandel, PhD, a current postdoc at UCSB in Montell’s group. “Integration is essential as any single stimulus is inadequate to differentiate humans from other,” the authors pointed out. “However, each of these cues have limitations,” Chandel added. The insects have poor vision, and a strong wind or rapid movement of the human host can throw off their tracking of the chemical senses. “… the efficacy of CO2 and olfactory cues in providing directional information is limited by air-current disturbances that exceed the mosquito’s flight speed, or if the host is moving quickly,” the researchers noted.

Within about 10 cm, these insects can detect the heat rising from our skin. And they can directly sense the temperature of our skin once they land. These two senses correspond to convection, heat carried away by a medium such as air, and conduction, which is heat via direct touch. These are two kinds of heat transfer.

Energy from heat can also travel longer distances when converted into electromagnetic waves, generally in the infrared (IR) range of the spectrum. The IR can then heat whatever it hits. Animals such as pit vipers can sense thermal IR from warm prey, and the team wondered whether mosquitoes, and specifically Ae. aegypti, also could detect thermal IR as a more reliable directional cue.

“Conductive heat requires contact, and convective heat is sensed at close range,” they noted. “Thus, if mosquitoes sense thermal IR radiation, then surface body temperature could be detected at greater distances, as radiant heat is not limited by the physical constraints of convection and conduction … Given the importance of multisensory integration in host-seeking, we wondered whether mosquitoes might exhibit attraction to thermal IR, but only in combination with other host cues.”

For their reported studies the researchers put female mosquitoes in a cage and measured their host-seeking activity in two zones. Each zone was exposed to human odors and CO2 at the same concentration that we exhale. However, only one zone was also exposed to IR from a source at skin temperature. A barrier separated the source from the chamber preventing heat exchange through conduction and convection. The team then counted how many mosquitoes began probing as if they were searching for a vein.

Adding thermal IR from a 34º C source (about skin temperature) doubled the insects’ host-seeking activity. And the team discovered it remains effective up to about 70 cm (2.5 feet). This makes infrared radiation a newly documented sense that mosquitoes use to locate us. “What struck me most about this work was just how strong of a cue IR ended up being,” DeBeaubien said. “Once we got all the parameters just right, the results were undeniably clear.”

Previous studies didn’t observe any effect of thermal infrared on mosquito behavior, but senior author Montell suspects this comes down to methodology. Scientists might try to isolate the effect of thermal IR on insects by only presenting an infrared signal without any other cues. “But any single cue alone doesn’t stimulate host-seeking activity. It’s only in the context of other cues, such as elevated CO2 and human odor that IR makes a difference,” said Montell. In fact, his team found the same thing in tests with only IR: infrared alone has no impact.

It isn’t possible for mosquitoes to detect thermal infrared radiation the same way they would detect visible light. The energy of IR is far too low to activate the rhodopsin proteins that detect visible light in animal eyes. Electromagnetic radiation with a wavelength longer than about 700 nm won’t activate rhodopsin, and IR generated from body heat is around 9,300 nm. “The thermal IR that emanates from surface body temperature is far lower in energy than the longest wavelengths that activate visual pigments,” the team noted. In fact, no known protein is activated by radiation with such long wavelengths, Montell said. But there is another way to detect IR.

Consider heat emitted by the sun. The heat is converted into IR, which streams through empty space. When the IR reaches Earth, it hits atoms in the atmosphere, transferring energy and warming the planet. “You have heat converted into electromagnetic waves, which is being converted back into heat,” Montell said. He noted that the IR coming from the sun has a different wavelength from the IR generated by our body heat, since the wavelength depends on the temperature of the source.

The authors considered that perhaps our body heat, which generates IR, might hit certain neurons in the mosquito, activating them by heating them. That would enable the mosquitoes to detect the radiation indirectly.

Scientists have known that the tips of a mosquito’s antennae have heat-sensing neurons. And the team discovered that removing these tips eliminated the mosquitoes’ ability to detect IR. “Rather than detecting photons directly, a more plausible mechanism for thermal IR detection is that the radiant energy warms dendrites in coeloconic sensilla near to the tip of the antenna, which in turn activates thermosensitive receptors,” the scientists further explained. “In support of this model, removal of the distal portion of the antenna, which contain heat-sensitive neurons, eliminates IR attraction.”

Pits at the end of the mosquito’s antennae shield the peg-like structures that detect thermal IR.
Pits at the end of the mosquito’s antennae shield the peg-like structures that detect thermal IR. [DeBeaubien and Chandel et al.]
Indeed, another lab found the temperature-sensitive protein, TRPA1, at the end of the antenna. And the UCSB team observed that animals without a functional trpA1 gene, which codes for the protein, couldn’t detect IR.

The tip of each antenna has peg-in-pit structures that are well adapted to sensing radiation. The pit shields the peg from conductive and convective heat, enabling the highly directional IR radiation to enter and warm the structure. “Located in a pit, the neurons would be largely protected from convective currents, and would receive radiant heat preferentially from the direction of the pit aperture,” the team noted.

The mosquito then uses TRPA1—essentially a temperature sensor—to detect infrared radiation. “We found that the heat-activated TRPA1 channel is expressed in neurons at the antennal tip and is required for responding to IR. By contrast, trpA1 mutants display normal attraction to conductive/convective heat in the temperature range of human skin … Our data support the model that TRPA1 senses IR at mid-range distances (~0.7 m) through the ‘warming neurons’ in the peg-in-pit sensilla.”

The activity of the heat-activated TRPA1 channel alone might not fully explain the range over which mosquitoes were able to detect IR. A sensor that exclusively relied on this protein may not be useful at the 70 cm range the team had observed. At this distance there likely isn’t sufficient IR collected by the peg-in-pit structure to heat it enough to activate TRPA1.

Fortunately, Montell’s group thought there might be more sensitive temperature receptors based on their previous work on fruit flies in 2011. They found a few proteins in the rhodopsin family that were quite sensitive to small increases in temperature. Although rhodopsins were originally thought of exclusively as light detectors, Montell’s group found that certain rhodopsins can be triggered by a variety of stimuli. They discovered that proteins in this group are quite versatile, involved not just in vision, but also in taste and temperature sensing. Upon further investigation, the researchers discovered that two of the 10 rhodopsins found in mosquitoes are expressed in the same antennal neurons as TRPA1.

Knocking out TRPA1 eliminated the mosquito’s sensitivity to IR. But insects with faults in either of the rhodopsins, Op1 or Op2, were unaffected. Even knocking out both the rhodopsins together didn’t entirely eliminate the animal’s sensitivity to IR, although it significantly weakened the sense. “Two opsins (op1, op2) and trpA1 are co-expressed at the end of the antenna, and mutations eliminating these opsins reduce IR sensation, but only at lower intensities of radiant heat,” the authors stated. “We propose that contributions of both opsins and TRPA1 to detecting radiant heat endows mosquitoes with a greater dynamic range for sensing radiant heating.”

Their results indicated that more intense thermal IR—like what a mosquito would experience at a closer range (for example, around one foot)—directly activates TRPA1. Meanwhile, Op1 and Op2 can get activated at lower levels of thermal IR, and then indirectly trigger TRPA1. “We suggest that, at higher IR intensities, the radiant heat is sufficient to directly activate TRPA1, while, at lower levels of thermal IR, activation of the opsins initiates a cascade that amplifies the signal and indirectly activates TRPA1,” the team stated. Since our skin temperature is constant, extending the sensitivity of TRPA1 effectively extends the range of the mosquito’s IR sensor to around 2.5 feet.

“In conclusion, thermal IR represents an important mid-range cue that is used by Ae. aegypti to couple longer- and shorter-range cues,” the authors wrote. “… we speculate that detection of the IR may be widely used among blood-feeding mosquitoes to home in on warm-blooded hosts.”

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