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Equine Alveolar Macrophage Response to Specific TLR Ligands: Effect of Exercise and Training
I. Waldschmidt
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Young race horses are frequently affected by respiratory diseases which could be due to an inappropriate innate immune response. Effects of training and exercise on immunity have been studied in human athletes and in horses but results are contradictory. Pulmonary alveolar macrophages (PAMs) are one of the principal actors of the pulmonary innate immunity. They recognize pathogens via Toll-like receptors (TLRs) which activate a downstream cascade leading to cytokine release. We hypothesized that training and exercise modify cytokine production in PAMs when stimulated with specific TLR ligands. Eight standardbred horses were trained during four months. Bronchoalveolar lavages (BALs) were performed before and after training, at rest and 24 hours after a standardized exercise test (SET). PAMs were isolated from BALs and stimulated with specific TLR ligands, ie FSL-1 for TLR2, Poly(I:C) for TLR3 and LPS for TLR4 . TLR expression was assessed by RT-PCR. Cytokine production before and after stimulation was quantified by ELISA. The SET did not induce any significant changes. On the opposite, a significant training-induced decrease in baseline TNF-α and IFN-β production was observed. Training induced a down-regulation of TLR3 expression and decreased Poly(I:C)-induced IFN-β and TNF-α release. TNF-α induced by FSL-1 stimulation was lower after training while no change in TLR2 expression was observed. LPS stimulation was not modified by training. This study suggested that training impairs pulmonary innate immune responses, especially anti-viral defense mechanisms. Our results could potentially explain the increased susceptibility of athletic horses to pulmonary diseases during training periods.
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