Cross-modal sensory compensation increases mosquito attraction to humans

Abstract

Sensory compensation is a process that allows individuals with a loss of one sense, for instance hearing or vision, to adapt to changes in their sensory abilities. Where this phenomenon has been observed, there is enhanced perception by another sense to compensate for deficiency of the lost sense. Such compensation is important for humans and non-human animals that use multisensory integration for effective navigation and the execution of vital tasks. Among these, female mosquitoes are sensory specialists that rely heavily on integrating multiple human-emitted cues in their quest for a suitable host to obtain a blood meal. Here, we identify a previously undescribed mechanism of sensory compensation in female Aedes aegypti mosquitoes. Mutant mosquitoes lacking the odorant receptor co-receptor Orco show specific enhancement in heat-seeking behavior. This sensory compensation does not require the antenna, which was previously assumed to be the primary mosquito thermosensitive organ. Instead, we found that the tips of the forelegs are required to detect heat, and that the heightened sensitivity in heat detection is mediated by increased neuronal activity in foreleg sensory neurons, which are distant from the head appendage neurons that express Orco. By comparative gene expression analysis in wildtype and Orco mutant legs, we identify Ir140, a foreleg-enriched member of the Ionotropic Receptor (IR) superfamily of sensory receptors, as strongly upregulated in Orco mutant legs. Emphasizing the important role of IRs in thermosensation, we find that mutant mosquitoes lacking the IR co-receptor, Ir25a, lose all responses to heat, and Ir140 mutants show strong deficits in responding to human skin temperatures. We generated an Ir140, Orco double mutant and show that these animals lose the remarkable sensory compensation seen in Orco mutants. This strongly suggests that upregulation of Ir140 in the foreleg is the mechanism of sensory compensation in Orco mutants. Odorant receptor expression is sparse in legs, suggesting an indirect, long-range mechanism of sensory compensation. Our findings reveal a novel compensatory mechanism in which loss of one sensory modality in female Aedes aegypti mosquitoes results in greater sensitivity in another to maintain the overall effectiveness of their host-seeking behavior, further enhancing their status as the most dangerous predator of humans.