Individual susceptibility to disgust modulates neural and systemic immune responses to virtual infections.

Disgust is a key psychological mechanism for avoiding pathogen exposure and constitutes a central component of the behavioral immune system. While disgust is thought to reduce infection risk through avoidance, it remains unclear how individual differences in disgust sensitivity shape downstream neuroimmune responses to perceived pathogen threats. Here, we show that lower disgust sensitivity is associated with stronger activation of type 1 innate lymphoid cells during exposure to infectious, compared with neutral, avatars in virtual reality. Disgust sensitivity further correlated with circulating signaling factors involved in immune regulation, including hormones related to the hypothalamic-pituitary-adrenal (HPA) axis, and eicosanoids. Linear models incorporating disgust sensitivity and threat exposure predicted these signaling factors, which in turn enabled accurate prediction of type 1 innate lymphoid cells responses using a pretrained neural network. Recreating this putative pathway, we were able to predict immune responses solely by disgust scores. Additionally, resting-state functional magnetic resonance imaging revealed that exposure to infectious avatars altered hypothalamic connectivity with brain regions involved in visual processing, peripersonal space representation, and social cognition, and these effects were modulated by individual disgust sensitivity. Together, these findings suggest that disgust sensitivity modulates multiple levels of the neuroimmune response to perceived pathogen threats. Across two complementary experiments, our results are consistent with a model linking sensory threat detection, hypothalamic signaling, and systemic immune activation. Rather than uniformly amplifying immune responses, higher disgust sensitivity appears to bias pathogen defense toward neural processing, whereas lower disgust sensitivity is associated with stronger physiological immune activation.