Heat and humidity sensors that alert mosquitoes to nearby human hosts

Abstract

Mosquito-borne diseases sicken >500,000,000 people annually, killing >500,0001. Mosquito host-seeking is guided by multiple host-associated cues, which combine to drive blood feeding in a manner that remains poorly understood2,3. While heat is a powerful mosquito attractant, recent studies indicate that disruption of heat seeking has little impact on host detection by the malaria vector Anopheles gambiae4, suggesting other cues act alongside heat in the complex sensory environment of a human host. Here we show mosquitoes require Ir93a (an Ionotropic Receptor5) to maintain attraction to a human host and feed on warmed blood. Using Ir93a, we uncover the previously uncharacterized mosquito hygrosensory system, and show Ir93a is required for humidity detection by humidity sensors (hygrosensors) as well as temperature detection by thermosensors, and for attraction to each stimulus. These findings indicate that hygrosensation and thermosensation function in parallel, driving host proximity detection in response to the overlapping heat and humidity gradients humans produce6,7. These host cue sensors appear to have arisen by co-opting existing sensors of physical cues rather than de novo, as Ir93a-dependent thermo- and hygro-sensors support physiological homeostasis in non-blood-feeding insects8-11. While Ir93a is conserved among arthropods, reliance on heat and humidity evolved independently in multiple blood-feeding lineages, suggesting multiple, vector-specific implementations of this common host-seeking strategy.

A spatial map of antennal-expressed olfactory ionotropic receptors in the malaria mosquito

“…In particular, IR75l and IR93a appear to be at least two-fold more highly expressed in their respective neurons compared to other IRs. IR93a has been linked to temperature and humidity-sensing in Drosophila and Anopheles (Knecht et al, 2016; Laursen et al, 2022), and an increased abundance might be required to mediate this affect. The functional role for IR75l remains to be determined.…”

“…However, the functional roles of mosquito IRs extend beyond sensing behaviorally relevant odorants. Several lines of evidence suggest multiple roles for insect IRs including oviposition cue detection (Chen and Amrein, 2017), courtship behavior (Grosjean et al, 2011), thermosensation (Greppi et al, 2020; Laursen et al, 2022), humidity detection (Knecht et al, 2016; Laursen et al, 2022), and taste sensation (Hussain et al, 2016; Jové et al, 2020). The diverse roles of IRs remain consistent with the widespread expression pattern across insect body parts.…”

Neurogenetic identification of mosquito sensory neurons

“…We also detected between 1 and 9 brp+ but Orco-negative neurons in proximal segment 1. These are likely the hygro- and thermo-sensory neurons that express Ir93a 19 .…”

“…While the identity of the Orco-negative antennal neurons is unknown, they most likely belong to neurons that express the IR olfactory receptor family, as reported by prior RNAseq studies 37 and recent in situ analysis 38 . Additionally, flagellomere segment 1 (the most proximal segment) contains only Orco-negative neurons, which likely include the ~22 Ir93a+ receptor neurons 19 .…”

“…The largest gene families of receptors involved in olfaction are Odorant Receptors (ORs), Ionotropic Receptors (IRs), and Gustatory Receptors (GRs). Current research focuses on the functional analysis of these receptors and creation of mutant mosquitoes targeting individual subunits or chemosensory co-receptors in order to determine their role in mosquito host-searching behavior [13][14][15][16][17][18][19][20][21][22][23] .…”