Science - USA (2020-02-07)

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CREDITS: (PHOTO) ALEXANDER WILD; (GRAPHIC) N. DESAI/

SCIENCE

imposed a strong selective force for genes

that confer resistance to malaria ( 3 , 4 ).

The complexity of the malaria parasite

makes development of a malaria vaccine a

difficult task. The development of resistance

to chemical agents in both mosquitoes to

insecticides and parasites to antiparasitic

drugs make imperative the search for new

tools and strategies. The rapid advance of

molecular and genomic sciences represents

a new hope for finding innovative solutions

with low environmental impact. In recent

years, several major biological mechanisms

have been unraveled in mosquitoes, in par-

ticular related to their sensory systems,

especially olfaction (smell). These studies re-

vealed conceivable molecular targets for in-

terfering with their ability to recognize and

locate human hosts ( 5 ).

However, animals do not usually rely on

just one sense for locating vital resources;

rather, they exploit all available information

that they can detect. Female mosquitoes are

not an exception; they exploit multimodal

information, such as sight, smell, heat, de-

tection of chemicals ( 6 – 8 ), and probably also

water vapor ( 9 ) for locating and recognizing

potential hosts, including humans (see the

figure). Thermoreception is a key sense in

insects and is particularly well-developed in

blood-sucking species ( 10 ). Thermal sensi-

tivity is provided by temperature-dependent

activation of specific molecular receptors

on the membrane of specialized cells in sen-

sory structures (sensilla) present in differ-

ent parts of the insect body, particularly the

antennae ( 11 , 12 ). These sensory cells con-

nect to the brain, informing on temperature

changes in the surrounding environment.

In mosquitoes, the heat emitted by the body

of warm-blooded vertebrates constitutes a

major cue for short-range orientation ( 13 ).

Greppi et al. uncovered a fundamental

piece of the mechanism of heat detection.

They show that the IR21a gene is essential

for the response to cooling of thermorecep-

tive cells in the antennae of A. gambiae. In

mutant mosquitoes with inactivated IR21a,

thermoreceptive cells no longer respond

to temperature changes. Consequently, the

ability of mutant mosquitoes to locate and

land on sources of a host temperature was

much reduced, as well as their responsive-

ness to the proximity of a human. Multi-

modal sensing often means that blocking

one input does not completely abolish the

response of an animal. Yet, the inactivation

of IR21a significantly reduces the ability of

female mosquitoes to find a food source.

Greppi et al. also characterized the sensory

cells that express IR21a. Their electrical ac-

tivity did not substantially vary between high

and low constant temperatures but strongly

reacted to temperature changes, increasing

firing when temperature decreased (cool-

ing cells). When the mosquito flies close to a

host, the heat flow on its antennae increases

or decreases with the distance and also the

temperature of receptors. The heat flow var-

ies nonlinearly with distance, meaning that

temperature changes are more marked at

the proximity of the target ( 10 ). That cool-

ing cells are activated by temperature varia-

tions, but not constant temperature, raises

the question of whether a mosquito could

measure the distance that separates it from

its host based on the activation dynamics of

these cells during the final approach. Such

measures seem to be taken by kissing bugs,

which extend their mouthparts at the reach

distance for biting, even in the absence of

any chemical, visual, or mechanical cue, us-

ing only thermal information ( 10 ).

Another interesting question raised by the

work of Greppi et al. is related to the evo-

lution of haematophagy (feeding on blood),

a way of life that occurs multiple times in

the evolutionary history of arthropods (in-

cluding mosquitoes) ( 14 ). That IR21a is con-

served across insects suggests repurposing of

an ancestral receptor from non–blood-suck-

ing Diptera. This receptor is also expressed

in sensory cells of the fruit fly (Drosophila

melanogaster). However, whereas Ir21a me-

diates heat avoidance in D. melanogaster,

Anopheles IR21a drives heat seeking and

heat-stimulated blood feeding ( 1 ). Other re-

ceptors are also involved in thermal orienta-

tion, particularly transient receptor potential

(TRP) channels. In mosquitoes, TRPA1 medi-

ates avoidance of temperatures higher than

those of a host. Understanding how these

different receptors contribute to thermosen-

sation in diverse blood-sucking species could

reveal how haematophagy evolved.

Thermoreception has been a relatively

neglected aspect of vector biology, with

research efforts focused largely on chemo-

reception. Odors play an important role in

insect biology and could be used to manipu-

late vector behavior. Thus, much more work

has been done on olfaction than any other

sensory system of mosquitoes. Recently,

however, interest for thermal sensation has

increased, opening research avenues and

perhaps revealing possibilities for control-

ling vector-borne diseases. j

REFERENCES AND NOTES

1. C. Greppi et al., Science 367 , 681 (2020).


2. World Health Organization (WHO), World Malaria Report
   2018 (WHO, 2018); http://www.who.int/malaria/ publications/
   world-malaria-report-2018/en.


3. P. W. Hedrick, Heredity 107 , 283 92011).


4. S. Sha, The Fever (S. Crichton Books, 2010).


5. L. B. Duvall et al., Cell 176 , 687 (2019).


6. C. J. McMeniman et al., Cell 156 , 1060 (2014).


7. F. van Breugel et al, Curr. Biol. 25 , 2123 (2015).


8. R. T. Cardé, Curr. Biol. 25 , R793 (2015).


9. F. E. Kellogg, J. Insect Physiol. 16 , 99 (1970).


10. C. R. Lazzari, Adv. Insect Physiol. 37 , 1 (2009).


11. G. Wang et al., Eur. J. Neurosci. 30 , 967 (2009).


12. R. A Corfas, L. B. Vosshall, eLife 4 , e.11750 (2015).


13. P. F. Zermoglio et al., J. Insect Physiol. 100 , 9 (2017).


14. M. J. Lehane, The Biology of Blood-Sucking in Insects
    (Cambridge, ed. 2, 2005).
    10.1126/science.aba4484

Activation Orientation Approach Landing Biting

Volatiles, air

currents, visual

features

Chemical

gradients, image

looming

Mechanical

contact,

tastants

Long range Short range

Heat

CO Water vapor

2

Female Anopholes gambiae

mosquitoes are vectors

of malaria parasites. They use

various senses to home-in

on targets, and blood-sucking

allows transfer of parasites.

7 FEBRUARY 2020 • VOL 367 ISSUE 6478 629

How mosquitoes find their hosts

Multimodal integration is essential for modulating general responsiveness, orientation, and approach. Carbon

dioxide stimulates the response to other cues, and heat detection is crucial for the final approach.

Published by AAAS