On Jul. 28, 2025, a study published in Nature Neuroscience shows that potential contact with approaching infectious avatars, entering the peripersonal space in virtual reality, are anticipated by multisensory–motor areas and activate the salience network, as measured with psychophysics, electroencephalography and functional magnetic resonance imaging. This proactive neural anticipation instigates changes in both the frequency and activation of innate lymphoid cells, mirroring responses seen in actual infections.

Alterations in connectivity patterns between infection-sensing brain regions and the hypothalamus, along with modulation of neural mediators, connect these effects to the hypothalamic–pituitary–adrenal axis. Neural network modeling recapitulates this neuro–immune cross-talk. These findings suggest an integrated neuro–immune reaction in humans toward infection threats, not solely following physical contact but already after breaching the functional boundary of body–environment interaction represented by the peripersonal space.

A vital function of an organism is to anticipate contact with threats to promptly activate a proper ‘fight-or-flight’ response. Mechanisms of predator detection and processing of threat imminence have been widely explored. Pathogens represent special forms of threats that must be detected and avoided. Through evolution, social species developed a series of behavioral responses, such as social distancing, aimed at preventing contacts and thus infections that have been termed the ‘behavioral immune system.

The researchers created a set of avatars showing clear signs of infection (infectious avatars) and two control conditions, namely neutral and fearful avatars (that is, an arousing but not pathogenic threatening stimulus). Results from explicit ratings, a seating distance scale and the Implicit Association Task demonstrated that infectious avatars were perceived as sick and contagious and evoked implicit avoidance responses compared to neutral and fearful avatars.

The research team’s integrated behavioral, neurophysiological, immunological and computational analyses provide a direct demonstration that potential infection threats (even when presented in VR) are processed by the PPS system and the salience network in an anticipatory way and preactivate the immune system by triggering ILC responses, likely via a nonlinear neuro–immune cross-talk involving the HPA axis.