Chronically raised glucocorticoids reduce innate immune function in Belding’s ground squirrels (Urocitellus beldingi) after an immune challenge

• Glucocorticoids were raised non-invasively in treatment squirrels for six days.
• Bacteria killing ability was used to measure innate immune function.
• The glucocorticoid treatment did not lower immune function.
• After the treatment, we gave squirrels an immune challenge.
• Treatment squirrels had lower immune function than controls after the challenge.

The hypothalamic–pituitary–adrenal (HPA) axis releases glucocorticoids (GCs), or stress hormones, during the vertebrate stress response. GCs can both enhance and suppress the immune system depending on whether the experienced stressor is acute or chronic and what aspect of immune function is measured. More research is needed to fully understand how the immune system reacts to stressors. In this study, we examined the effects of chronically raised GCs on innate immune function in Belding’s ground squirrels (Urocitellus beldingi). We measured immune function with a bacteria killing ability (BKA) assay, an integrative and functional assessment of an animal’s ability to clear a bacterial infection. All studies to date have examined how acute stressors or repeated social stressors impact BKA. This study is the first to our knowledge to investigate how chronically raised GCs impact BKA both before and after an immune challenge. We noninvasively raised GCs in treatment squirrels for six days and then gave them, and a group of untreated (control) squirrels, an injection of lipopolysaccharide (LPS) to stimulate their innate immune system. Treatment squirrels exhibited lower BKA after, but not before, being challenged with LPS. These results suggest that experiencing chronic stress may not be detrimental to immune functioning until an individual is challenged with an infection.