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.