Doctoral thesis (Dissertations and theses)
Training alters the innate immune response in the lower airway of horses
Frellstedt, Linda
2014
 

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Keywords :
immunity; TLR; equine
Abstract :
[en] Many human and animal studies have examined various markers of the innate and/or adaptive immunity in association with exercise and have come to the general conclusion that exercise, either acute or chronic, modifies the immune response. Regular moderate exercise has beneficial and protective effects on immunity because it results in a balance of pro- and anti-inflammatory effects. This balance may be disturbed during exhaustive exercise, such as that experienced during competition and overtraining, resulting in immunosuppression. Humans frequently suffer from upper respiratory tract infections after prolonged intense exercise, whereas horses suffer primarily from lower airway inflammation and/or infection. The underlying mechanism for this difference remains unknown at this time. The sampling of different cell types is limited in humans and therefore, these studies focus on the evaluation of cells in peripheral blood or markers in saliva. Two groups of researchers in human sports medicine have compared populations of sedentary and regularly exercising people. The expression of Toll-like receptors (TLRs) 1, 2, 3 and 4 was decreased in peripheral blood monocytes in exercising subjects. This altered expression of TLRs was also associated with a lower production of pro-inflammatory cytokines (IL-6, IL-1α, TNF-α). Regular exercise induced circulating anti-inflammatory cytokines (IL-10, IL-6) and, therefore, limited the effects of pro-inflammatory cytokines. The first line of defense in the airways is provided by pulmonary alveolar macrophages and bronchial epithelial cells. Strenuous exercise impairs the viability of bronchial epithelial cells, reduces the viral defense mechanisms, and decreases oxidative burst activity of pulmonary alveolar macrophages. The altered immune response in association with exercise/training does not only lead to an increased risk for infection but may also cause the development of allergies and chronic inflammation in the lower airway. This may explain why young equine athletes frequently suffer from Inflammatory Airway Disease (IAD). The etiology of IAD remains unknown but an association with subclinical viral infections as well as inflammatory stimuli from the environment has been suspected. The objective of this work was to increase our knowledge of immune mechanisms in young equine athletes by evaluating the effect of acute exercise and training on the innate immune responses of pulmonary alveolar macrophages (PAM), bronchial epithelial cells (BEC) and monocytes. The hypothesis was that exercise and training modify the TLR mRNA expression as well as the production of pro-inflammatory cytokines and interferons in these three cell types. Eight Standardbred horses were studied over a period of 9 months during which they were acclimatized, trained and deconditioned. Standardized exercise tests were performed regularly and biological samples (blood, bronchoalveolar lavages, and biopsies of the bronchial epithelium) were taken at defined intervals in order to allow a longitudinal evaluation of the different parameters. Monocytes, PAM and BEC were harvested and analyzed. The expression of TLR3 was decreased in equine PAM and monocytes after a period of training, but not after a single strenuous exercise session. In addition, the expression of TLR4 was increased in equine monocytes after training. The production of TNF-α and IFN-β was also examined in PAM and monocytes ex vivo after the stimulation with different TLR ligands. The production of these cytokines was reduced in PAM after a defined period of training and remained decreased for three months thereafter. In contrast, the synthesis of TNF-α was increased after a period of training in equine monocytes and remained increased thereafter. In a second study, a model for the culture of equine bronchial epithelial cells (EBEC) was developed which allowed us to evaluate the effect of exercise and training on the innate immune response of these cells. Acute exercise or training did not alter the TLR mRNA expression in EBEC. The production of IFN-β was increased in EBEC from trained horses after stimulation with a TLR3 ligand. Concurrently, the secretion of TNF-α and IL-6 was impaired in EBEC from trained horses after the stimulation with TLR2 and TLR3 ligands. This study focused on a single aspect of the innate immunity in horses, gaining knowledge of the TLR expression in three cell types and their response to specific TLR agonists. These results have to be considered in the global context of the innate immunity remembering that they represent only a small part of the complex immune system. Only one type of training (Standardbred race training) and one model of acute exercise (standardized exercise test on a treadmill) were evaluated in this study. This should be considered when drawing conclusions, because it is currently understood that the effects on immune responses vary with different types, intensity and duration of exercise and/or training. Nonetheless, this work has established that a local immunosuppression develops within the lungs in trained horses, and may explain the increased susceptibility of exercising horses to pulmonary viral infections. This local immunosuppression is associated with an increased potential of monocytes to produce pro-inflammatory cytokines when challenged with pathogens. The effects of exercise on innate immunity are complex and further studies are needed to continue the work in this field. In addition to the response to training in young sport horses, a number of environmental factors associated with their nutrition and housing may play important roles in the development of pulmonary infections and inflammation (e.g. IAD). To confirm the significance of the presented results, it would be interesting to investigate the innate immune response in trained horses when challenged with equine pathogens, such as equine influenza and equine herpesviruses. The ultimate goal of this work and other studies in the future is to develop immuno-modulating molecules that could be used for the prevention and treatment of equine respiratory diseases.
Research center :
Physiology; CEMESPO
Disciplines :
Anatomy (cytology, histology, embryology...) & physiology
Veterinary medicine & animal health
Author, co-author :
Frellstedt, Linda ;  Université de Liège - ULiège > Département de sciences fonctionnelles > Phys. neuro-muscul., de l'effort - Méd. sport. des animaux
Language :
English
Title :
Training alters the innate immune response in the lower airway of horses
Alternative titles :
[fr] L’entrainement modifie la reponse immunitaire innee dans les voies respiratoires profondes chez le cheval
Defense date :
23 October 2014
Number of pages :
181
Institution :
ULiège - Université de Liège
Degree :
Doctorat en Sciences Vétérinaires
Promotor :
Art, Tatiana ;  Université de Liège - ULiège > UDI Faculté de médecine vétérinaire
Jury member :
Mc GORUM, Bruce
NAUWYNCK, Hans J.
Amory, Hélène ;  Université de Liège - ULiège > Département d'Enseignement et de Clinique des Equidés (DCE) > Médecine interne des équidés
Gillet, Laurent  ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Peeters, Dominique ;  Université de Liège - ULiège > Département d'Enseignement et de Clinique des animaux de Compagnie (DCC) > Médecine interne des animaux de compagnie
Vanderplasschen, Alain ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire
Funders :
University of Liege; FEDER; FUI; CRBN; Hippolia Foundation
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since 25 September 2014

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