Cross-modal sensory compensation increases mosquito attraction to humans.

Sensory compensation occurs when loss of one sense leads to enhanced perception by another sense. We have identified a previously undescribed mechanism of sensory compensation in female mosquitoes. Odorant receptor co-receptor () mutants show enhanced attraction to human skin temperature and increased heat-evoked neuronal activity in foreleg sensory neurons. , a foreleg-enriched member of the ionotropic receptor (IR) superfamily of sensory receptors, is up-regulated in mutant legs. , double mutants do not show the enhanced heat seeking seen in single mutants, suggesting that up-regulation of in the foreleg is a key mechanism underlying sensory compensation in mutants. Because expression is sparse in legs, this sensory compensation requires an indirect, long-range mechanism. Our findings highlight how female mosquitoes, despite suffering olfactory sensory loss, maintain the overall effectiveness of their host-seeking behavior by up-regulating attraction to human skin temperature, further enhancing their status as the most dangerous predator of humans.