Scare or care? How immunological processes shape perception of sickness-relevant stimuli in humans

Humans and other animals have developed several defense systems to handle living in a pathogen-rich world. These defense systems include immune responses, as well as behavioral responses aimed at supporting immune functions during the fight against the infection, called sickness behavior. Since sickness behavior is believed to be adaptive, it is possible that sickness shifts perception of the world depending on the priorities and needs of the sick individual. For instance, sick humans in general avoid social interactions to save energy, but can also approach specific people that can provide care and support. However, these ambivalent aspects of sickness behavior are understudied. Thus, the aim of this thesis was to investigate perception of sickness-relevant stimuli, and how such perception is modulated during immune activation. In particular, we assessed how immune activation affected cognitive reappraisal of emotions to unpleasant stimuli (Study I), if naïve observers can detect sick others and if this ability is affected by immune activation (Studies II-III), and if immune activation affects perception of unfamiliar caregivers (Study IV).

In four studies, we used the model of experimental endotoxemia, consisting in intravenously injecting a low dose of the bacterial endotoxin lipopolysaccharide (LPS) into healthy volunteers. The recognition of LPS by immune cells triggers inflammatory responses, and causes a transient state of sickness for a few hours, allowing studying sickness behavior in an experimental setting. In Study I, participants received an LPS or a saline (placebo) injection, and completed a task in which they were asked to down-regulate or up-regulate their emotions in response to general negative and disgust stimuli. We showed that sick participants reported a greater success in down-regulating their emotions to general negative and disgust stimuli, compared to healthy participants. In Studies II-III, we used sickness detection tasks, in which naïve observers rated the health status of stimuli consisting of photos of faces and video recordings from a walking task obtained from the participants in Study I. In Study II, naïve observers could detect sick others solely from the way they walked. In Study III, participants performed a sickness detection task, once when sick (LPS injection) and once when healthy (no injection). We showed that, when sick themselves, individuals categorized more healthy walkers as sick, and were thus less good at discriminating between sick and healthy walkers, compared to when healthy. In Study IV, we developed the Caregiver Perception Task (CgPT), which participants completed when sick (LPS injection) and when healthy (saline injection). The findings revealed that sick participants were more willing to receive care from unfamiliar care providers, compared to when healthy.

This thesis adds to the current knowledge on social sickness behavior. Altogether, these findings highlight that sickness is not all about perceiving the world as more negative. Yes, sick individuals may categorize others more easily as threats, but sickness can also possibly increase the ability to feel less negative emotions, together with making some items and individuals in the environment more appealing (e.g., caregivers). Future studies need to investigate how such changes in perception of sickness-relevant stimuli translate into behavior.

List of scientific papers

I. Hansson LS, Axelsson J, Petrovic P, Paues Göranson S, Olsson MJ, Lekander M/Lasselin J. (2021). Regulation of emotions during experimental endotoxemia: A pilot study. Brain, Behavior, and Immunity. 93, 420-424.
https://doi.org/10.1016/j.bbi.2021.01.013

II. Hansson LS/Lasselin J, Tognetti A, Axelsson J, Olsson MJ, Sundelin T/Lekander M. (2023). The walking sick: Perception of experimental sickness from biological motion. Brain, Behavior, and Immunity. 113, 319-327.
https://doi.org/10.1016/j.bbi.2023.07.020

III. Hansson LS, Tognetti A, Tavakoli E , Stache J, Kakeeto M, Melin J, Bredin S, Skarp R, Lensmar C, Demand R, Olsson MJ, Wilhelms DB, Toll John R, Jensen K, Lekander M/Lasselin J. Identifying sick people while sick yourself: a study of identification of facial cues and walking patterns of sick individuals during experimental endotoxemia. [Manuscript]

IV. Hansson LS, Tognetti A, Sigurjónsson P, Brück E, Wåhlén K, Jensen K, Olsson MJ, Toll John R, Wilhelms DB, Lekander M/Lasselin J. Perception of unfamiliar caregivers during sickness – using the new Caregiver Perception Task (CgPT) during experimental endotoxemia. [Accepted]