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Abstract
Bronchopneumonia caused by Rhodococcus equi (R. equi) occurs in a narrow age window in foals. On farms endemic for R. equi pneumonia, individual responses to the bacteria are inconsistent. Currently, a biomarker to predict disease susceptibility and severity has not yet been identified. Steroid hormones, like cortisol and vitamin D, modulate immune responses. Age-related differences in cortisol and vitamin D predispose the neonatal foal to the risk of developing severe disease in other bacterial infections. Steroid hormone-regulated immune responses, in other species, are vital, for the clearance of intracellular bacteria. Immunoregulation by vitamin D and cortisol may play a role in foal R. equi susceptibility.
The aim of this work was to examine the role of age-associated changes in vitamin D, cortisol, and the inflammatory cytokines they regulate in relation to R. equi disease. First, we characterized vitamin D receptor (VDR) expression within equine alveolar macrophages (AMφ), the cell involved in primary R. equi respiratory infection and showed age-associated differences in VDR expression between foals and adults. Second, we characterized VDR expression and cytokine protein production in response to ex vivo R.equi infection of AMφ. VDR expression was downregulated in response to R. equi in AMφ from adult horses but unchanged in AMφ cells from young foals. Age- and R. equi-associated cytokine production in AMφ cells from four-week-old foals was equivalent to responses from adult horse cells. These findings support our hypothesis that the vitamin D/VDR pathway is involved in immune regulation within equine leukocytes.
Lastly, we wanted to determine if an age- and disease-associated effect on vitamin D and cortisol concentrations is present in foals naturally exposed to R. equi on an endemic farm. Furthermore, we hoped that concentration differences in cytokines and steroid hormones would predict disease severity in pneumonic foals. This study elucidated age-associated differences in steroid hormones and cytokines, but these differences did not predict disease susceptibility and severity in pneumonic foals. However, these age-associated differences provide information to better understand foal immunity. Disease-associated differences in interferon (IFN)-γ concentrations indicate that the mechanisms and kinetics of cytokine production may play a role in disease susceptibility.