The effect of cortisol on equine monocyte-derived dendritic cell phenotype and cytokine production

BackgroundIncreased risk of infection in neonates, including foals, is associated with the naivety of the immune system and the immaturity of the endocrine system. Foal dendritic cells (DCs) are phenotypically and functionally less mature than adult horse DCs. Exposure of foal DCs to foal plasma alters DC phenotypic maturation, cytokine secretion and bacterial endocytosis. Specific plasma factors that impact equine DC activity are unknown. Endocrine dysfunction, resulting in altered cortisol availability, is common in foals. Cortisol impacts DC maturation and function in other species, but the effect of cortisol on equine DCs is not described. We hypothesized that exposure to cortisol would impact both the phenotype and function of equine monocyte-derived DCs (MoDCs), perpetuating an immature phenotype and altered cytokine profile.MethodsMoDCs were generated from foals (n = 8) on 1, 7 and 30 days of age and adult horses (n = 9). MoDCs were exposed to killed bacteria in the presence or absence of cortisol. The expression of surface markers (MHC class-II, CD86 and CD14) was measured by flow cytometry. Supernatant cytokine concentrations (IL-4, IL-17, IFN-gamma and IL-10) were quantified using a validated bead-based immunoassay.ResultsCortisol exposure reduced the percentage of equine MoDCs expressing MHC class-II and CD86 (p <= 0.03). Adult horse MoDCs exposed to bacteria and cortisol produced less IL-4, IL-17, IFN-gamma and IL-10 than cells not treated with cortisol, and foal MoDCs secreted less IL-10 and IL-4 (p <= 0.009).ConclusionsIn sum, cortisol exposure perpetuates an immature MoDC phenotype and alters cytokine responses, which might impact the foal's susceptibility to infection. Increased risk of infection in foals is associated with the immune system's naivety and the endocrine system's immaturity. In this study, cortisol used at a concentration observed in septic foals perpetuated dendritic immaturity. The altered cortisol dynamics in foals impacting dendritic cell function might contribute to their susceptibility to bacterial infection. dagger image