Cellular and Molecular Basis of Odorant Reception in the Biting Midge Forcipomyia taiwana
摘要
Biting midges are medically significant pests whose bites trigger dermatitis and systemic allergic responses while transmitting diverse pathogens, thereby posing a severe threat to human health. How these and other blood-feeding insects parse complex odor environments to locate hosts while avoiding unfavorable cues is a fundamental question in sensory biology. However, the olfactory mechanisms underlying odorant detection in midges remain poorly understood. Here, we elucidate the neural and molecular mechanisms underlying odor-guided behavior in Forcipomyia taiwana, the predominant biting midge in China and Southeast Asia, using an integrated, multi-scale approach. The antennae contain diverse olfactory sensilla and a broad chemoreceptor repertoire that respond to host- and plant-derived volatiles. In contrast, spherical sensilla within the maxillary palp form a dual-channel olfactory pathway that segregates two ecologically salient classes of chemical information: one sensory neuron is strongly activated by host-associated CO2 and the other is preferentially tuned to plant-derived terpenoids. Tissue-resolved transcriptomics, receptor localization, and heterologous functional analysis identify the palp-enriched receptor FtaiOr1 as a strong molecular determinant of this terpenoid-sensitive pathway while FtaiOr27 and FtaiOr60 localize to the antennae and detect additional odor classes. These peripheral sensory responses correspond to opposing behavioral outcomes: terpenoids, including camphor, eucalyptol, and (+)-fenchone, strongly repel F. taiwana, whereas human-associated volatiles such as butanal and butanoic acid promote attraction. Together, these findings link receptor identity, neuronal coding, and behavior in an understudied hematophagous insect, revealing a mechanistic framework for understanding odor-guided behavior in biting midges and suggests broader principles by which blood-feeding Diptera partition ecologically opposing olfactory information.
参考文献
F. Sick, M. Beer, H. Kampen, K. Wernike, Culicoides Biting Midges—Underestimated Vectors for Arboviruses of Public Health and Veterinary Importance. Viruses 11, 376 (2019).
H. Kampen, D. Werner, Biting midges (Diptera: Ceratopogonidae) as vectors of viruses. Microorganisms 11, 2706 (2023).
F. G. Naveca et al., Human outbreaks of a novel reassortant Oropouche virus in the Brazilian Amazon region. Nat. Med. 30, 3509–3521 (2024).
H. M. Moreira et al., Outbreak of Oropouche virus in frontier regions in western Amazon. Microbiol. Spectr. 12, e01629 (2024).
C. Alkan, T. Ikegami, Emerging threat of Oropouche virus: clinical features, experimental models, and virulence. Virulence 17, 2664956 (2026).
L. Subissi et al., Oropouche virus: transmission, epidemiology, genetic diversity, and public health implications. eClinicalMedicine 95, 103871 (2026).
A. Touati, T. Idres, C. De Champs, N. S. Basher, Emerging arthropod-borne infections in temperate regions: comparative synthesis across mosquitoes, ticks, sandflies, and biting midges. Insects 17, 311 (2026).
L. Harrup, M. A. Miranda, S. Carpenter, Advances in control techniques for Culicoides and future prospects. Vet. Ital. 52, 247–264 (2016).
S. Carpenter, P. S. Mellor, S. J. Torr, Control techniques for Culicoides biting midges and their application in the U.K. and northwestern Palaearctic. Med. Vet. Entomol. 22, 175–187 (2008).
J. B. Pitzer et al., Assessing permethrin susceptibility of field-collected biting midges in Florida and evidence for resistance evolution using laboratory selections. Med. Vet. Entomol. (2026).
G. Gibson, S. J. Torr, Visual and olfactory responses of haematophagous Diptera to host stimuli. Med. Vet. Entomol. 13, 2–23 (1999).
F. Guidobaldi, I. J. May-Concha, P. G. Guerenstein, Morphology and physiology of the olfactory system of blood-feeding insects. J. Physiol. Paris 108, 96–111 (2014).
T. Lu, Y. Zhang, D. Gou, H. Chen, X. Hou, The effects of human volatiles produced by skin microbiota on Forcipomyia (Lasiohelea) taiwana host preference. Pest Manag. Sci. 81, 7815–7826 (2025).
C. Montell, The sensory arsenal mosquitoes use to find us. Trends Parasitol. 41, 591–602 (2025).
J. Fleischer, P. Pregitzer, H. Breer, J. Krieger, Access to the odor world: olfactory receptors and their role for signal transduction in insects. Cell. Mol. Life Sci. 75, 485–508 (2018).
C. J. McMeniman, R. A. Corfas, B. J. Matthews, S. A. Ritchie, L. B. Vosshall, Multimodal integration of carbon dioxide and other sensory cues drives mosquito attraction to humans. Cell 156, 1060–1071 (2014).
M. Herre et al., Non-canonical odor coding in the mosquito. Cell 185, 3104–3123.e3128 (2022).
M. C. Stensmyr et al., A conserved dedicated olfactory circuit for detecting harmful microbes in Drosophila. Cell 151, 1345–1357 (2012).
A. F. Carey, G. Wang, C. Y. Su, L. J. Zwiebel, J. R. Carlson, Odorant reception in the malaria mosquito Anopheles gambiae. Nature 464, 66–71 (2010).
E. A. Hallem, J. R. Carlson, Coding of odors by a receptor repertoire. Cell 125, 143–160 (2006).
E. Isberg, Y. Hillbur, R. Ignell, Comparative study of antennal and maxillary palp olfactory sensilla of female biting midges (Diptera: Ceratopogonidae: Culicoides) in the context of host preference and phylogeny. J. Med. Entomol. 50, 485–492 (2013).
G. Sollai, P. Solari, C. Masala, R. Crnjar, A. Liscia, Effects of avermectins on olfactory responses of Culicoides imicola (Diptera: Ceratopogonidae). J. Med. Entomol. 44, 656–659 (2007).
A. Bhasin, A. J. Mordue, W. Mordue, Electrophysiological and behavioural identification of host kairomones as olfactory cues for Culicoides impunctatus and C. nubeculosus. Physiol. Entomol. 25, 6–16 (2000).
M. D. Lin et al., Decoding the genome of bloodsucking midge Forcipomyia taiwana (Diptera: Ceratopogonidae): insights into odorant receptor expansion. Insect Biochem. Mol. Biol. 168, 104115 (2024).
A. Borkent, P. Dominiak, Catalog of the biting midges of the world (Diptera: Ceratopogonidae). Zootaxa 4787, 1–377 (2020).
Y. Yu, Important hematophagous midges of China. Science Press, Beijing (2019).
Y. Chen et al., Hypersensitivity to Forcipomyia taiwana (biting midge): clinical analysis and identification of major For t 1, For t 2 and For t 3 allergens. Allergy 60, 1518–1523 (2005).
H. Shu, C. Chen, Y. Hsu, G. Lin, A pilot study for the establishment of a bloodsucking model for Forcipomyia taiwana (biting midge). Int. J. Clin. Med. Microbiol. 2, 118 (2017).
C. Chen, J. Lien, Y. Lin, S. Hsu, The diurnal biting pattern of a bloodsucking midge Forcipomyia (Lasiohelea) taiwana (Shiraki) (Diptera: Ceratopogonidae). Chin. J. Microbiol. Immunol. 14, 54–56 (1981).
Y. H. Chen, G. Y. Hwang, P. C. Chen, W. C. Tu, M. F. Lee, Molecular cloning and immunologic characterization of For t 2: a major allergen from the biting midge Forcipomyia taiwana. Allergy 66, 703–705 (2011).
X. L. Guo, Z. H. Yang, Research progress on vectors of Japanese encephalitis in China. Chin. J. Vector Biol. Control 30, 106–110 (2019).
J. R. Wu, S. Y. Wu, Isolation of Japanese encephalitis virus from Lasiohelea taiwana (Ceratopogonidae). Acta Microbiol. Sin. 5, 22–26 (1957).
U. R. Bernier, D. L. Kline, D. R. Barnard, C. E. Schreck, R. A. Yost, Analysis of human skin emanations by gas chromatography/mass spectrometry. 2. Identification of volatile compounds that are candidate attractants for the yellow fever mosquito Aedes aegypti. Anal. Chem. 72, 747–756 (2000).
J. M. Kembro, R. H. Marin, J. A. Zygadlo, R. M. Gleiser, Effects of the essential oils of Lippia turbinata and Lippia polystachya (Verbenaceae) on the temporal pattern of locomotion of the mosquito Culex quinquefasciatus (Diptera: Culicidae) larvae. Parasitol. Res. 104, 1119–1127 (2009).
Y. Vainer et al., Sensory coding of borneol repellency in culicine mosquitoes via the Or49 pathway. Nat. Commun. 17, 2981 (2026).
F. Liu, Z. Ye, A. Baker, H. Sun, L. J. Zwiebel, Gene editing reveals obligate and modulatory components of the CO₂ receptor complex in the malaria vector mosquito, Anopheles coluzzii. Insect Biochem. Mol. Biol. 127, 103470 (2020).
P. L. Jones, G. M. Pask, D. C. Rinker, L. J. Zwiebel, Functional agonism of insect odorant receptor ion channels. Proc. Natl. Acad. Sci. U.S.A. 108, 8821–8825 (2011).
D. K. Yadav, S. Rathee, V. Sharma, U. K. Patil, A comprehensive review on insect repellent agents: medicinal plants and synthetic compounds. Anti-Inflamm. Anti-Allergy Agents Med. Chem. 24, 84–102 (2025).
P. C. Page, K. Labuschagne, J. P. Nurton, G. J. Venter, A. J. Guthrie, Duration of repellency of N,N-diethyl-3-methylbenzamide, citronella oil and cypermethrin against Culicoides species when applied to polyester mesh. Vet. Parasitol. 163, 105–109 (2009).
C. R. Lazzari, Why do repellents repel? Curr. Opin. Insect Sci. 66, 101277 (2024).
N. K. T. Thomas, C. Berry, I. S. Sobhy, Making scents of mosquito lures: semiochemical attractants for adult mosquitoes. Parasites Vectors (2026).
W. Liu, S. Lee, E. Yang, Evaluation for attractiveness of four chemicals to the biting midge, Forcipomyia taiwana (Diptera: Ceratopogonidae). J. Am. Mosq. Control Assoc. 25, 448–455 (2009).
J. G. Logan et al., Identification of human-derived volatile chemicals that interfere with attraction of Aedes aegypti mosquitoes. J. Chem. Ecol. 34, 308–322 (2008).
Y. T. Qiu, J. J. A. van Loon, W. Takken, J. Meijerink, H. M. Smid, Olfactory coding in antennal neurons of the malaria mosquito, Anopheles gambiae. Chem. Senses 31, 845–863 (2006).
M. Ghaninia, R. Ignell, B. S. Hansson, Functional classification and central nervous projections of olfactory receptor neurons housed in antennal trichoid sensilla of female yellow fever mosquitoes, Aedes aegypti. Eur. J. Neurosci. 26, 1611–1623 (2007).
N. M. Stanczyk, J. F. Y. Brookfield, R. Ignell, J. G. Logan, L. M. Field, Behavioral insensitivity to DEET in Aedes aegypti is a genetically determined trait residing in changes in sensillum function. Proc. Natl. Acad. Sci. U.S.A. 107, 8575–8580 (2010).
R. Benton, K. S. Vannice, C. Gomez-Diaz, L. B. Vosshall, Variant ionotropic glutamate receptors as chemosensory receptors in Drosophila. Cell 136, 149–162 (2009).
Z. Ye, F. Liu, H. Sun, A. P. Baker, L. J. Zwiebel, Discrete roles of Ir76b ionotropic coreceptor impact olfaction, blood feeding, and mating in the malaria vector mosquito Anopheles coluzzii. Proc. Natl. Acad. Sci. U.S.A. 119, e2112385119 (2022).
T. Lu et al., Odor coding in the maxillary palp of the malaria vector mosquito Anopheles gambiae. Curr. Biol. 17, 1533–1544 (2007).
G. Wang, A. F. Carey, J. R. Carlson, L. J. Zwiebel, Molecular basis of odor coding in the malaria vector mosquito Anopheles gambiae. Proc. Natl. Acad. Sci. U.S.A. 107, 4418–4423 (2010).
X. Wang et al., Heterologous expression and functional analysis of Aedes aegypti odorant receptors to human odors in Xenopus oocytes. J. Vis. Exp. 172, e61813 (2021).
F. Miazzi et al., Optimization of insect odorant receptor trafficking and functional expression via transient transfection in HEK293 cells. Chem. Senses 44, 673–682 (2019).
J. H. Pettersson, A. M. Cattaneo, Heterologous investigation of metabotropic and ionotropic odorant receptors in ab3A neurons of Drosophila melanogaster. Front. Mol. Biosci. 10, 1275901 (2024).
A. Ysobel et al., A review on the potential and efficacy of plant-based mosquito repellents against DEET-based mosquito repellents. In SHS Research Conference Proceedings (De La Salle University, Manila) (2022).
W. Wu et al., Study of the repellent activity of 60 essential oils and their main constituents against Aedes albopictus, and nano-formulation development. Insects 13, 1077 (2022).
J. G. Logan, M. A. Birkett, Semiochemicals for biting fly control: their identification and exploitation. Pest Manag. Sci. 63, 647–657 (2007).
L. Dormont, M. Mulatier, D. Carrasco, A. Cohuet, Mosquito attractants. J. Chem. Ecol. 47, 351–393 (2021).
R. Yan et al., Molecular and functional characterization of a conserved odorant receptor from Aedes albopictus. Parasites Vectors 15, 43 (2022).
M. A. de Souza et al., Adulticide and repellent activity of essential oils against Aedes aegypti (Diptera: Culicidae) – a review. S. Afr. J. Bot. 124, 160–165 (2019).
H. Zhang et al., A volatile from the skin microbiota of flavivirus-infected hosts promotes mosquito attractiveness. Cell 185, 2510–2522.e16 (2022).
E. J. Huang, J. Q. Zhang, Y. S. Cai, Y. H. Zhong, B. Gao, Application of COⅠ and 16S rDNA genes in the identification of Lasiohelea taiwana. China Port Sci. Technol. 2, 4–8 (2021).
J. Pelletier, A. Guidolin, Z. Syed, A. J. Cornel, W. S. Leal, Knockdown of a mosquito odorant-binding protein involved in the sensitive detection of oviposition attractants. J. Chem. Ecol. 36, 245–248 (2010).
F. Liu et al., A dual-target molecular mechanism of pyrethrum repellency against mosquitoes. Nat. Commun. 12, 2553 (2021).
Z. Li, M. Li, J. Wang, Asymmetric subgenomic chromatin architecture impacts on gene expression in resynthesized and natural allopolyploid Brassica napus. Commun. Biol. 5, 762 (2022).
A. Poulet, A. J. Kratkiewicz, D. Li, J. C. van Wolfswinkel, Chromatin analysis of adult pluripotent stem cells reveals a unique stemness maintenance strategy. Sci. Adv. 9, eadh4887 (2023).
J. S. Chahda et al., The molecular and cellular basis of olfactory response to tsetse fly attractants. PLoS Genet. 15, e1008005 (2019).
X. Wang et al., DEET olfactory reception in the yellow fever mosquito. Preprint, LangTaoSha Preprint Server (2026).
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