Mosquito heat seeking is driven by an ancestral cooling receptor

doi:10.1126/science.aay9847

. 2020 Feb 7;367(6478):681-684.

doi: 10.1126/science.aay9847.

Mosquito heat seeking is driven by an ancestral cooling receptor

Chloe Greppi ^#¹, Willem J Laursen ^#¹, Gonzalo Budelli ¹, Elaine C Chang ¹, Abigail M Daniels ¹, Lena van Giesen ¹, Andrea L Smidler ^{2

3}, Flaminia Catteruccia ², Paul A Garrity ⁴

Affiliations

¹ Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA.
² Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
³ Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
⁴ Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA. pgarrity@brandeis.edu.

^# Contributed equally.

PMID: 32029627
PMCID: PMC8092076
DOI: 10.1126/science.aay9847

Mosquito heat seeking is driven by an ancestral cooling receptor

Chloe Greppi et al. Science. 2020.

. 2020 Feb 7;367(6478):681-684.

doi: 10.1126/science.aay9847.

Authors

Chloe Greppi ^#¹, Willem J Laursen ^#¹, Gonzalo Budelli ¹, Elaine C Chang ¹, Abigail M Daniels ¹, Lena van Giesen ¹, Andrea L Smidler ^{2

3}, Flaminia Catteruccia ², Paul A Garrity ⁴

Affiliations

¹ Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA.
² Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, MA 02115, USA.
³ Wyss Institute for Biologically Inspired Engineering, Boston, MA 02115, USA.
⁴ Department of Biology and Volen Center for Complex Systems, Brandeis University, Waltham, MA 02453, USA. pgarrity@brandeis.edu.

^# Contributed equally.

PMID: 32029627
PMCID: PMC8092076
DOI: 10.1126/science.aay9847

Abstract

Mosquitoes transmit pathogens that kill >700,000 people annually. These insects use body heat to locate and feed on warm-blooded hosts, but the molecular basis of such behavior is unknown. Here, we identify ionotropic receptor IR21a, a receptor conserved throughout insects, as a key mediator of heat seeking in the malaria vector Anopheles gambiae Although Ir21a mediates heat avoidance in Drosophila, we find it drives heat seeking and heat-stimulated blood feeding in Anopheles At a cellular level, Ir21a is essential for the detection of cooling, suggesting that during evolution mosquito heat seeking relied on cooling-mediated repulsion. Our data indicate that the evolution of blood feeding in Anopheles involves repurposing an ancestral thermoreceptor from non-blood-feeding Diptera.

PubMed Disclaimer

Conflict of interest statement

Competing interests:

A.L.S. is a co-inventor on patent WO2015105928A1 (WIPO PCT; pending; inventors: K. Esvelt and A.L. Smidler) "Rna-guided gene drives". Patent involves spreading desirable traits genetically through mosquito populations using Cas9-based gene drives. IR21a could potentially be used as a target for such a gene drive. P.A.G. is a co-inventor on patent WO2017196861A1 (WIPO PCT; pending; inventors: Z. Knecht, P.Garrity, Lina Ni) "Methods for modulating insect hygro- and/or thermosensation". This patent proposes using members of the Ionotropic Receptor family as targets for strategies to disrupt hygro- and thermosensation in insects.

Figures

Fig. 1.

Fig. 1.. IR21a is expressed in the antennal tip.

(A) Upper, Ir21a locus. Middle, Ir21a^+7bp mutations (blue). Lower, virtual translations, with 450 C-terminal amino acids of wild-type IR21a replaced by 24 novel amino acids (blue) and premature stop in Ir21a^+7bp. (B) Targeted integration generating Ir21a^EYFP. Lower: Combined bright-field/fluorescent illumination (left) and molecular genotyping (right) of Ir21a⁺ and Ir21a^EYFP homozygotes. m, markers. (C ) Mosquito anterior (drawing based on ref. (27)). Inset, flagellomere 13. D,E, wild type (D) and Ir21a^+7bp (E) female immunostaining, flagellomere 13. wild type, n=13 animals stained, Ir21a^+7bp n=7. IR21a-expressing cell bodies (asterisks), sensory endings (arrows). Anti-HRP labels neuronal membrane proteins. DAPI labels nuclei.

Fig. 2:

Fig. 2:. Ir21a is required for thermosensing.

(A) Recording electrode insertion site. (B) Representative recordings, indicated regions displayed on expanded time scale. Circles, spikes. Weighted average spike rate, instantaneous spike frequency smoothed using 1s triangular window. Dotted lines, spike thresholds. (C) Peri-stimulus time histograms (average +/− SEM). wild type, n=8 animals tested for 30°C/25°C; others, n=6. One heating/cooling trial per animal. (D) Cooling response = (average Hz 0.2s-0.7s after cooling onset) – (average Hz 5s-10s pre-cooling). Heating response = (average Hz 0.5s-1.5s after heating onset) – (average Hz 5s-10s pre-heating). Letters, distinct groups (Tukey HSD, alpha=0.01, except 32°C➔37°C, alpha=0.05). Shapiro-Wilk and ANOVA test values are provided in statistics section of methods.

Fig. 3:

Fig. 3:. Ir21a mediates heat-seeking.

(A) Heat-seeking assay. Assay box is 28 cm deep, 40 cm long and 16 cm tall. (B) Upper, stimulus sequence. Lower, Heat Seeking Index. (C) Representative images of 26°C (blue) and 37°C (red) targets before (upper) and ~120 s after (lower) CO₂ pulse initiation in wild type. (D-E) ~120 s after CO₂ pulse initiation in Ir21a^EYFP (D) and Ir21a^+7bp (E). (F) Landing on 37°C and 26°C targets as percent of mosquitoes taking flight. Average +/− SEM. wild type n=15 independent groups, Ir21a^EYFP n=6, Ir21a^+7bp n=7. 42–52 females/group. (G) Heat seeking index (average from 105s to 135s). Letters denote distinct categories (Steel-Dwass test, p<0.01). Shapiro-Wilk, Kruskal-Wallis and Steel-Dwass test values are provided in statistics section of methods.

Fig. 4:

Fig. 4:. Ir21a promotes warmth-stimulated blood feeding.

(A-E) Host approach. Mosquitoes were activated by five breaths, then presented a hand. (B) Mosquitoes landed (accumulated) on cage roof below hand. Average +/− SEM. 33–75 females/assay. wild type, n=19 independent groups; Ir21a^EYFP , n=21. (C) Average accumulation, 180s to 300s. (D) Accumulation rate=[{(accumulation at 45s) – (accumulation pre-hand exposure)}/{(maximum accumulation) – (accumulation pre-hand exposure)}]/45s. (E) Departure rate=[1 – {(accumulation at 340s)/(accumulation at 300s)}]/40s. (F-H) Blood-feeding. Two meals (one dyed green) placed on cage. (G) RT meal dyed. (H) Warm meal dyed. Dotted lines link pairs. 33-75 females/assay. n=6 independent groups/genotype, except H, Ir21a^EYFP n=7. p values indicate t-test results. The green tracking dye partially reduced relative consumption of the meals to which it was added. Cages are 17.5 cm-sided cubes. Shapiro-Wilk test values are provided in statistics section of methods.

See this image and copyright information in PMC

Comment in

In the heat of the night.
Lazzari CR. Lazzari CR. Science. 2020 Feb 7;367(6478):628-629. doi: 10.1126/science.aba4484. Science. 2020. PMID: 32029616 No abstract available.

References

1. World, Health, Organization, A global brief on vector-borne diseases. WHO/DCO/WHD/2014.1 (2014).
1. Brown AWA, The attraction of mosquitoes to hosts. Journal of the American Medical Association 196, 159–162 (1966). - PubMed
1. Carde RT, Multi-Cue Integration: How Female Mosquitoes Locate a Human Host. Current biology : CB 25, R793–795 (2015). - PubMed
1. Lazzari CR, The thermal sense of blood-sucking insects: why physics matters. Curr Opin Insect Sci 34, 112–116 (2019). - PubMed
1. Howlett FM, The influence of temperature upon the biting of mosquitoes. Parasitology 3, 479– 484 (1910).

Publication types

Actions
Actions

MeSH terms

Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions
Actions

Substances

Actions

Grants and funding

LinkOut - more resources

Full Text Sources
Other Literature Sources
- Dryad Digital Repository
Molecular Biology Databases
- Gene Ontology

[1] World, Health, Organization, A global brief on vector-borne diseases. WHO/DCO/WHD/2014.1 (2014).

[2] World, Health, Organization, A global brief on vector-borne diseases. WHO/DCO/WHD/2014.1 (2014).

[3] Brown AWA, The attraction of mosquitoes to hosts. Journal of the American Medical Association 196, 159–162 (1966). - PubMed

[4] Brown AWA, The attraction of mosquitoes to hosts. Journal of the American Medical Association 196, 159–162 (1966). - PubMed

[5] Carde RT, Multi-Cue Integration: How Female Mosquitoes Locate a Human Host. Current biology : CB 25, R793–795 (2015). - PubMed

[6] Carde RT, Multi-Cue Integration: How Female Mosquitoes Locate a Human Host. Current biology : CB 25, R793–795 (2015). - PubMed

[7] Lazzari CR, The thermal sense of blood-sucking insects: why physics matters. Curr Opin Insect Sci 34, 112–116 (2019). - PubMed

[8] Lazzari CR, The thermal sense of blood-sucking insects: why physics matters. Curr Opin Insect Sci 34, 112–116 (2019). - PubMed

[9] Howlett FM, The influence of temperature upon the biting of mosquitoes. Parasitology 3, 479– 484 (1910).

[10] Howlett FM, The influence of temperature upon the biting of mosquitoes. Parasitology 3, 479– 484 (1910).

Account

Save citation to file

Email citation

Add to Collections

Add to My Bibliography

Your saved search

Create a file for external citation management software

Your RSS Feed

Mosquito heat seeking is driven by an ancestral cooling receptor

Affiliations

Mosquito heat seeking is driven by an ancestral cooling receptor

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

Comment in

References

Publication types

MeSH terms

Substances

Grants and funding

LinkOut - more resources

Full Text Sources

Other Literature Sources

Molecular Biology Databases