Multimodal Integration of Carbon Dioxide and Other Sensory Cues Drives Mosquito Attraction to Humans

Multiple sensory cues emanating from humans are thought to guide blood-feeding female mosquitoes to a host. To determine the relative contribution of carbon dioxide (CO2) detection to mosquito host-seeking behavior, we mutated the AaegGr3 gene, a subunit of the heteromeric CO2 receptor in Aedes aegypti mosquitoes. Gr3 mutants lack electrophysiological and behavioral responses to CO2. These mutants also fail to show CO2-evoked responses to heat and lactic acid, a human-derived attractant, suggesting that CO2 can gate responses to other sensory stimuli. Whereas attraction of Gr3 mutants to live humans in a large semi-field environment was only slightly impaired, responses to an animal host were greatly reduced in a spatial-scale-dependent manner. Synergistic integration of heat and odor cues likely drive host-seeking behavior in the absence of CO2 detection. We reveal a networked series of interactions by which multimodal integration of CO2, human odor, and heat orchestrates mosquito attraction to humans.

[1]  Geier,et al.  Influence of odour plume structure on upwind flight of mosquitoes towards hosts , 1999, The Journal of experimental biology.

[2]  G. Gibson,et al.  Visual and olfactory responses of haematophagous Diptera to host stimuli , 1999, Medical and veterinary entomology.

[3]  B. Nelson,et al.  The role of proboscis of the malaria vector mosquito Anopheles stephensi in host-seeking behavior , 2011, Parasites & Vectors.

[4]  R. J. Pitts,et al.  Molecular characterization of the Aedes aegypti odorant receptor gene family , 2007, Insect molecular biology.

[5]  P. A. Woke Cold-blooded Vertebrates as Hosts for Aëdes aegypti Linn. , 1937 .

[6]  M. Copland,et al.  Activation of Anopheles gambiae mosquitoes by carbon dioxide and human breath , 1995, Medical and veterinary entomology.

[7]  B. Marshall,et al.  UNIDENTIFIED CURVED BACILLI ON GASTRIC EPITHELIUM IN ACTIVE CHRONIC GASTRITIS , 1983, The Lancet.

[8]  M. Beroza,et al.  L-Lactic Acid: A Mosquito Attractant Isolated from Humans , 1968, Science.

[9]  S. Ritchie,et al.  A Secure Semi-Field System for the Study of Aedes aegypti , 2011, PLoS neglected tropical diseases.

[10]  Paul C. Jepson,et al.  Host location by Aedes aegypti (Diptera: Culicidae): a wind tunnel study of chemical cues , 1991 .

[11]  Leslie B. Vosshall,et al.  Variant Ionotropic Glutamate Receptors as Chemosensory Receptors in Drosophila , 2009, Cell.

[12]  T. R. Rao,et al.  Diel periodicity in the landing of Aedes aegypti on man. , 1973, Bulletin of the World Health Organization.

[13]  Ring T. Cardé,et al.  Moment-to-moment flight manoeuvres of the female yellow fever mosquito (Aedes aegypti L.) in response to plumes of carbon dioxide and human skin odour , 2011, Journal of Experimental Biology.

[14]  D. Small Flavor is in the brain , 2012, Physiology & Behavior.

[15]  R N Cox,et al.  Aerodynamics of the human microenvironment. , 1969, Lancet.

[16]  Ruth Campbell,et al.  The processing of audio-visual speech: empirical and neural bases , 2008, Philosophical Transactions of the Royal Society B: Biological Sciences.

[17]  Leslie B. Vosshall,et al.  Two chemosensory receptors together mediate carbon dioxide detection in Drosophila , 2007, Nature.

[18]  W. Takken,et al.  Central projections of olfactory receptor neurons from single antennal and palpal sensilla in mosquitoes. , 2003, Arthropod structure & development.

[19]  S. Boyle,et al.  Targeting a Dual Detector of Skin and CO2 to Modify Mosquito Host Seeking , 2013, Cell.

[20]  Willem Takken,et al.  Sweaty skin: an invitation to bite? , 2011, Trends in parasitology.

[21]  L. Burgess Probing Behaviour of Ædes ægypti (L.) in Response to Heat and Moisture , 1959, Nature.

[22]  John R. Carlson,et al.  The molecular basis of CO2 reception in Drosophila , 2007, Proceedings of the National Academy of Sciences.

[23]  M. Geier,et al.  Carbon dioxide instantly sensitizes female yellow fever mosquitoes to human skin odours , 2005, Journal of Experimental Biology.

[24]  C. Wysocki,et al.  Analyses of volatile organic compounds from human skin , 2008, The British journal of dermatology.

[25]  M. Gillies.,et al.  The Role of Carbon Dioxide in Host-Finding by Mosquitoes (Diptera: Culicidae): A Review , 1980 .

[26]  Nan Li,et al.  Ultra-prolonged activation of CO2-sensing neurons disorients mosquitoes , 2011, Nature.

[27]  W. Takken,et al.  Odor Coding in the Maxillary Palp of the Malaria Vector Mosquito Anopheles gambiae , 2007, Current Biology.

[28]  S. McIver,et al.  Fine structure of pegs on the palps of female culicine mosquitoes. , 1972, Canadian journal of zoology.

[29]  J. Kennedy The Visual Responses of Flying Mosquitoes. , 2009 .

[30]  Lucas P. J. J. Noldus,et al.  A 3D Analysis of Flight Behavior of Anopheles gambiae sensu stricto Malaria Mosquitoes in Response to Human Odor and Heat , 2013, PloS one.

[31]  T. Kröber,et al.  An In Vitro Assay for Testing Mosquito Repellents Employing a Warm Body and Carbon Dioxide as a Behavioral Activator , 2010, Journal of the American Mosquito Control Association.

[32]  T. Hocking,et al.  Heritable Targeted Gene Disruption in Zebrafish Using Designed Zinc Finger Nucleases , 2008, Nature Biotechnology.

[33]  S. Whyard,et al.  Functional validation of the carbon dioxide receptor genes in Aedes aegypti mosquitoes using RNA interference , 2012, Insect molecular biology.

[34]  Z. Adelman,et al.  Validation of novel promoter sequences derived from two endogenous ubiquitin genes in transgenic Aedes aegypti , 2010, Insect molecular biology.

[35]  L. Vosshall,et al.  Single Sensillum Recordings in the Insects Drosophila melanogaster and Anopheles gambiae , 2010, Journal of visualized experiments : JoVE.

[36]  Leslie B. Vosshall,et al.  Or83b Encodes a Broadly Expressed Odorant Receptor Essential for Drosophila Olfaction , 2004, Neuron.

[37]  D. Malaspina,et al.  Hidden consequences of olfactory dysfunction: a patient report series , 2013, BMC Ear, Nose and Throat Disorders.

[38]  R. O'connell,et al.  Electrophysiological responses of receptor neurons in mosquito maxillary palp sensilla to carbon dioxide , 1995, Journal of Comparative Physiology A.

[39]  D. Robert,et al.  Tracking of flying insects using pan-tilt cameras , 2000, Journal of Neuroscience Methods.

[40]  D. Huson,et al.  Dendroscope 3: an interactive tool for rooted phylogenetic trees and networks. , 2012, Systematic biology.

[41]  H. Robertson,et al.  Evolution of the Gene Lineage Encoding the Carbon Dioxide Receptor in Insects , 2009, Journal of insect science.

[42]  L. Zwiebel,et al.  Functional agonism of insect odorant receptor ion channels , 2011, Proceedings of the National Academy of Sciences.

[43]  W. F. Snow The effect of a reduction in expired carbon dioxide on the attractiveness of human subjects to mosquitoes. , 1970 .

[44]  Richard Axel,et al.  A dimorphic pheromone circuit in Drosophila from sensory input to descending output , 2010, Nature.

[45]  A. James,et al.  orco mutant mosquitoes lose strong preference for humans and are not repelled by volatile DEET , 2013, Nature.