Abstract

Body odors change with health status and the odors of sick animals can induce avoidance behaviors in healthy conspecifics. Exposure to sickness odors might also alter the physiology of healthy conspecifics and modify the odors they produce. We hypothesized that exposure to odors of sick (but non-infectious) animals would alter the odors of healthy cagemates. To induce sickness, we injected mice with a bacterial endotoxin, lipopolysaccharide. We used behavioral odor discrimination assays and analytical chemistry techniques followed by predictive classification modeling to ask about differences in volatile odorants produced by two types of healthy mice: those cohoused with healthy conspecifics and those cohoused with sick conspecifics. Mice trained in Y-maze behavioral assays to discriminate between the odors of healthy versus sick mice also discriminated between the odors of healthy mice cohoused with sick conspecifics and odors of healthy mice cohoused with healthy conspecifics. Chemical analyses paired with statistical modeling revealed a parallel phenomenon. Urine volatiles of healthy mice cohoused with sick partners were more likely to be classified as those of sick rather than healthy mice based on discriminant model predictions. Sickness-related odors could have cascading effects on neuroendocrine or immune responses of healthy conspecifics, and could affect individual behaviors, social dynamics, and pathogen spread.

Highlights

  • Living in groups can increase access to resources such as food, shelter, and mates[1], but can impose direct costs on individuals, such as increased competition, greater conspicuousness to predators, and higher risk of infections transmitted from conspecifics[1,2,3,4,5]

  • Healthy mice were injected with a volume-matched placebo, consisting of a sterile phosphate-buffered saline (PBS) solution, which does not induce sickness behaviors or activate inflammatory immune responses, but which controlled for the effects of handling and the injection procedure across experimental animals

  • Healthy mouse odors might change in the presence of sick conspecifics if sensory cues indicating a possible risk of a transmission event activate immunological defenses[49] or induce a neuroendocrine stress response to a perceived threat to homeostasis

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Summary

Introduction

Living in groups can increase access to resources such as food, shelter, and mates[1], but can impose direct costs on individuals, such as increased competition, greater conspicuousness to predators, and higher risk of infections transmitted from conspecifics[1,2,3,4,5]. Most of these behavioral assessments of responses to the odors of LPS-injected individuals have involved presentation of odor stimuli (e.g., live animals or their urine or bedding material) within 4 hours of injection[20,32,35,40] This early time point following LPS injection is associated with robust pro-inflammatory immune responses, increased body temperature (fever), and the expression of sickness behaviors such as lethargy, anorexia, and self-isolation[23,41,42,43]. It is unknown whether avoidance or constrained social investigation of sick animals and their odors by healthy conspecifics persists beyond early www.nature.com/scientificreports/. Healthy mouse odors might change in the presence of sick conspecifics if sensory cues indicating a possible risk of a transmission event activate immunological defenses[49] or induce a neuroendocrine stress response to a perceived threat to homeostasis

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