The Effect of Race Training on the Basal Gene Expression of Alveolar Macrophages Derived From Standardbred Racehorses

Abstract

Mild to moderate equine asthma is prevalent in young racehorses, particularly early in their training period. Although the precise aetiopathogenesis remains undetermined, it is possible that the susceptibility of this population might partly reflect an exercise-associated immune derangement at the level of the airway. We performed a genome-wide basal gene expression scan on alveolar macrophages (AMs) isolated from Standardbred racehorses prior to and after commencement of competition race training with a view to identifying any exerciseassociated gene expression modulation consistent with functional alterations which might reflect training-associated immunological derangement. Microarray technology was used to analyse the basal gene expression profiles of bronchoalveolar fluid-derived AMs, harvested from six systemically healthy Standardbred racehorses prior to (T0) and following (T1) entry into training. Additionally, AM LPS-induced TNF-α and IL-10 release at T0 and T1 was assessed. Although the data revealed significant inter-horse heterogeneity in relation to the magnitude of individual gene expression at each time-point, within each horse, several inflammatory related genes (e.g. chemokine ligands, interferons and NFKB) declined in expression from T0 to T1. Entry into training did not significantly alter AM LPS-induced TNF-α or IL-10 release. The data support a direct effect of training on AM basal gene expression, particularly with respect to immune-related genes. The pattern of trainingassociated differential gene expression may indicate relative downregulation of inflammatory-related genes, consistent with an immunosuppressive effect of training and an increased susceptibility to opportunistic pathogens.

The equine mononuclear phagocyte system: The relevance of the horse as a model for understanding human innate immunity

“…Both an exercise‐associated reduction in equine AM phagocytic capacity 179 and a training‐associated derangement in the responsiveness of equine AMs to various TLR ligands have been reported, theoretically reflecting an increased susceptibility to opportunistic infection 178 . In agreement, we recently demonstrated a training‐associated alteration in equine AM basal gene expression, which was also consistent with a degree of immunosuppression at the level of the airways 180 …”

“…231,232 Despite localisation of inflammation to the airways in MMEA, 171 few studies have assessed the influence of training on immune cell function specifically at this anatomical site, a key consideration in light of the previously mentioned disassociation between the response of equine monocytes and AMs to training. 178,180 As with many domesticated animals, selective breeding of horses has produced an array of breeds with specific traits relating to appearance (size and colour), temperament and performance (speed, strength and gait), resulting in more than 450 different breeds with a significant degree of diversity. 233,234 Given the nature of (OMIA: https://omia.org/home/).…”

“…This phenomenon, known as the ‘ open window ’ theory, reflects a temporal association between intense exercise and increased susceptibility to opportunistic infection 231,232 . Despite localisation of inflammation to the airways in MMEA, 171 few studies have assessed the influence of training on immune cell function specifically at this anatomical site, a key consideration in light of the previously mentioned disassociation between the response of equine monocytes and AMs to training 178,180 …”

Training-Associated Alterations In Equine Respiratory Immunity – A Multi-Omics Comparative Approach.

“…Both an exercise-associated reduction in equine AM phagocytic capacity (12) and a training-associated derangement in the responsiveness of equine AMs to various TLR ligands have been reported, theoretically re ecting increased susceptibility to opportunistic infection (10). In agreement, we recently demonstrated a training-associated alteration in equine AM basal gene expression, and con rmed a degree of immunomodulation at the level of the airways (11). Consequently, there appears to be su cient justi cation for further de ning the link between training and airway immunity.…”

“…The well recognized association between high intensity exercise and symptoms of respiratory infection amongst human athletes has fueled interest in the impact of training on immune function (8,9). Despite localization of in ammation to the airways in MMEA (7), few studies have assessed the in uence of training on immune cell function speci cally at this anatomical site, a key consideration in light of the recently reported disassociation between the response of blood derived equine monocytes and alveolar macrophages (AMs) to training (10,11). Both an exercise-associated reduction in equine AM phagocytic capacity (12) and a training-associated derangement in the responsiveness of equine AMs to various TLR ligands have been reported, theoretically re ecting increased susceptibility to opportunistic infection (10).…”