Decoding the Bite: Sensory cues, host heterogeneity, and pathogen manipulation in mosquito host-seeking behavior

Mosquitoes, primarily females, require blood meals for reproduction, making them prolific biters and major vectors of diseases such as malaria, dengue, Zika, and West Nile. This review synthesizes the mechanisms driving mosquito host-seeking behavior and the factors underlying heterogeneous human biting patterns. Mosquitoes locate hosts via a suite of sensory cues: long-range attraction to CO₂, followed by visual, thermal, and close-range olfactory cues. Olfaction is dominated by receptors that detect volatile organic compounds (VOCs) from human skin, sweat, and the microbiota. Host selection exhibits significant heterogeneity and is influenced by human physiological factors, including age (children/elderly individuals are often more attractive), sex (inconsistently reported), larger body size (higher metabolic output), pregnancy (increased CO₂, temperature, and VOCs), and skin/clothing color (dark colors that are more attractive). While some studies suggest blood type preferences (e.g., O for Ae. albopictus, B for Ae. aegypti), findings are inconsistent. Behavioral factors such as alcohol consumption increase attraction, whereas defensive behaviors reduce biting success. Crucially, pathogens manipulate host attractiveness: malaria (Plasmodium) increases the levels of aldehydes and terpenes via mechanisms involving HMBPP, and dengue/Zika increases acetophenone production via changes in the skin microbiota, increasing mosquito attraction and disease transmission. Mosquito host preference exhibits plasticity, shifting due to host availability (e.g., bird migration for West Nile vectors) or interventions (e.g., bed nets). Understanding these mechanisms (sensory cues, host factors, pathogen manipulation, and plasticity) is vital for developing targeted interventions (personal protection, odor masking, housing modifications, and microbiota management) to reduce bites and disease transmission.