[en] In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs), co-stimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because the innate immunity plays an essential role in lung defense mechanisms, we aimed to assess the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAM) were collected from horses in an untrained, moderately and intensively trained as well as deconditioned state before and after a strenuous exercise test (SET). The cells were analysed for TLR mRNA expression by real-time PCR in vitro and the cytokine production after in vitro stimulation with TLR ligands was measured by ELISA. Our results showed that training, but not acute exercise, modified the innate immune responses in both compartments. The mRNA expression of TLR3 was down-regulated by training in both cell types, whereas the expression of TLR4 was up-regulated in monocytes. Monocytes treated with lipopolysaccharide (LPS) and a synthetic diacylated lipoprotein (FSL) showed increased cytokine secretion in trained and deconditioned subjects indicating the activation of cells at the systemic level. The production of TNF-alpha and IFN-beta in non-stimulated and stimulated PAM was decreased in trained and deconditioned horses and might therefore explain the increased susceptibility to respiratory infections. Our study reports a dissociation between the systemic and the lung response to training that is probably implicated in the systemic inflammation and in the pulmonary susceptibility to infection.
Research Center/Unit :
FARAH - Fundamental and Applied Research for Animals and Health - ULiège
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
Waldschmidt, Ingrid; National Veterinary School Alfort, CIRALE, Goustranville, France
Gosset, Philippe; Institut de Pasteur de Lille, CIIL, Lille, France
Desmet, Christophe ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Pirottin, Dimitri ; Université de Liège - ULiège > Département de sciences fonctionnelles > Département de sciences fonctionnelles
Bureau, Fabrice ; Université de Liège - ULiège > Département de sciences fonctionnelles > GIGA-R : Biochimie et biologie moléculaire
Farnir, Frédéric ; Université de Liège - ULiège > Département de productions animales > Biostatistiques et bioinformatique appliquées aux sc. vétér.
Franck, Thierry ; Université de Liège - ULiège > Centre for Oxygen, Research & Development (CORD)
Dupuis-Tricaud, Marie-Capucine; National Veterinary School Alfort, CIRALE, Goustranville, France
Lekeux, Pierre ; Université de Liège - ULiège > Département de sciences fonctionnelles > Physiologie
Art, Tatiana ; Université de Liège - ULiège > Département de sciences fonctionnelles > Phys. neuro-muscul., de l'effort - Méd. sport. des animaux
Language :
English
Title :
Training Modifies Innate Immune Responses in Blood Monocytes and in Pulmonary Alveolar Macrophages
Publication date :
2014
Journal title :
American Journal of Respiratory Cell and Molecular Biology
ISSN :
1044-1549
eISSN :
1535-4989
Publisher :
American Thoracic Society, New York, United States - New York
Nieman DC. Is infection risk linked to exercise workload? Med Sci Sports Exerc 2000; 32(7 Suppl):S406-S411. (Pubitemid 30482640)
Gleeson M, Walsh NP; British Association of Sport and Exercise Sciences. The BASES expert statement on exercise, immunity, and infection. J Sports Sci 2012;30:321-324.
Pedersen BK, Toft AD. Effects of exercise on lymphocytes and cytokines. Br J Sports Med 2000;34:246-251. (Pubitemid 30609522)
Davis JM, Kohut ML, Colbert LH, Jackson DA, Ghaffar A, Mayer EP. Exercise, alveolar macrophage function, and susceptibility to respiratory infection. J Appl Physiol (1985) 1997;83:1461-1466.
Nieman DC. Exercise immunology: practical applications. Int J Sports Med 1997;18:S91-S100.
Nieman DC. Risk of upper respiratory tract infection in athletes: an epidemiologic and immunologic perspective. J Athl Train 1997;32:344-349. (Pubitemid 127530241)
Gleeson M, McFarlin B, Flynn M. Exercise and Toll-like receptors. Exerc Immunol Rev 2006;12:34-53.
Akira S, Uematsu S, Takeuchi O. Pathogen recognition and innate immunity. Cell 2006;124:783-801. (Pubitemid 43261452)
Suzuki K, Yamada M, Kurakake S, Okamura N, Yamaya K, Liu Q, Kudoh S, Kowatari K, Nakaji S, Sugawara K. Circulating cytokines and hormones with immunosuppressive but neutrophil-priming potentials rise after endurance exercise in humans. Eur J Appl Physiol 2000;81:281-287. (Pubitemid 30189950)
Morgado JM, Rama L, Silva I, de Jesus Inácio M, Henriques A, Laranjeira P, Pedreiro S, Rosado F, Alves F, Gleeson M, et al. Cytokine production by monocytes, neutrophils, and dendritic cells is hampered by long-term intensive training in elite swimmers. Eur J Appl Physiol 2012;112:471-482.
Pyne DB, Gleeson M. Effects of intensive exercise training on immunity in athletes. Int J Sports Med 1998;19(Suppl 3):S183-S191; discussion S191-S194.
Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, et al. Position statement. Part one: immune function and exercise. Exerc Immunol Rev 2011;17:6-63.
Nieman DC. Immune response to heavy exertion. J Appl Physiol (1985) 1997;82:1385-1394.
Lancaster GI, Khan Q, Drysdale P, Wallace F, Jeukendrup AE, Drayson MT, Gleeson M. The physiological regulation of toll-like receptor expression and function in humans. J Physiol 2005;563:945-955. (Pubitemid 40425607)
Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK. Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 1999;515:287-291. (Pubitemid 29092641)
Burrell MH, Wood JL, Whitwell KE, Chanter N, Mackintosh ME, Mumford JA. Respiratory disease in thoroughbred horses in training: the relationships between disease and viruses, bacteria and environment. Vet Rec 1996;139:308-313. (Pubitemid 126614389)
Wood JL, Newton JR, Chanter N, Mumford JA. Association between respiratory disease and bacterial and viral infections in British racehorses. J Clin Microbiol 2005;43:120-126. (Pubitemid 40096288)
Wood JL, Newton JR, Chanter N, Mumford JA. Inflammatory airway disease, nasal discharge and respiratory infections in young British racehorses. Equine Vet J 2005;37:236-242. (Pubitemid 40655932)
Allen KJ, Tremaine WH, Franklin SH. Prevalence of inflammatory airway disease in national hunt horses referred for investigation of poor athletic performance. Equine Vet J Suppl 2006;36:529-534.
Richard EA, Fortier GD, Pitel PH, Dupuis MC, Valette JP, Art T, Denoix JM, Lekeux PM, Erck EV. Sub-clinical diseases affecting performance in Standardbred trotters: diagnostic methods and predictive parameters. Vet J 2010;184:282-289.
Rossdale PD, Hopes R, Digby NJ, offord K. Epidemiological study of wastage among racehorses 1982 and 1983. Vet Rec 1985;116:66-69.
Noakes TD. Implications of exercise testing for prediction of athletic performance: a contemporary perspective. Med Sci Sports Exerc 1988;20:319-330. (Pubitemid 18266110)
Rose RJ, Hodgson DR, Kelso TB, McCutcheon LJ, Reid TA, Bayly WM, Gollnick PD. Maximum O2 uptake, O2 debt and deficit, and muscle metabolites in Thoroughbred horses. J Appl Physiol (1985) 1988;64:781-788.
Snow DH, Vogel CJ. Equine fitness: the care and training of the athletic horse. Newton Abbott, Devon, UK: David and Charles, Inc.; 1987.
Evans DL, Rose RJ. Cardiovascular and respiratory responses in Thoroughbred horses during treadmill exercise. J Exp Biol 1988;134:397-408. (Pubitemid 18052216)
Noakes TD. Lore of running. Cape Town, South Africa: Oxford University Press; 1992.
Waldschmidt I, Pirottin D, Art T, Audigié F, Bureau F, Tosi I, El Abbas S, Farnir F, Richard E, Dupuis MC. Experimental model of equine alveolar macrophage stimulation with TLR ligands. Vet Immunol Immunopathol 2013;155:30-37.
McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Stewart LK, Timmerman KL, Coen PM. Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. J Gerontol A Biol Sci Med Sci 2006;61:388-393.
.McFarlin BK, FlynnMG, CampbellWW, Stewart LK, Timmerman KL. TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Med Sci Sports Exerc 2004;36:1876-1883. (Pubitemid 39473505)
Oliveira M, Gleeson M. The influence of prolonged cycling on monocyte Toll-like receptor 2 and 4 expression in healthy men. Eur J Appl Physiol 2010;109:251-257.
Timmerman KL, Flynn MG, Coen PM, Markofski MM, Pence BD. Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise? J Leukoc Biol 2008;84:1271-1278.
Stewart LK, Flynn MG, Campbell WW, Craig BA, Robinson JP, McFarlin BK, Timmerman KL, Coen PM, Felker J, Talbert E. In fluence of exercise training and age on CD14+ cell-surface expression of toll-like receptor 2 and 4. Brain Behav Immun 2005;19:389-397. (Pubitemid 41074777)
Flynn MG, McFarlin BK, Phillips MD, Stewart LK, Timmerman KL. Toll-like receptor 4 and CD14 mRNA expression are lower in resistive exercise-trained elderly women. J Appl Physiol (1985) 2003;95:1833-1842.
Christley RM, Hodgson DR, Rose RJ, Hodgson JL, Wood JL, Reid SW. Coughing in thoroughbred racehorses: risk factors and tracheal endoscopic and cytological findings. Vet Rec 2001;148:99-104. (Pubitemid 33605406)
Semple PL, Binder AB, Davids M, Maredza A, van Zyl-Smit RN, Dheda K. Regulatory T cells attenuate mycobacterial stasis in alveolar and blood-derived macrophages from patients with tuberculosis. Am J Respir Crit Care Med 2013;187:1249-1258.
Kirby AC, Newton DJ, Carding SR, Kaye PM. Pulmonary dendritic cells and alveolar macrophages are regulated by gammadelta T cells during the resolution of S. pneumoniae-induced inflammation. J Pathol 2007;212:29-37. (Pubitemid 46746287)
Wilsher S, Allen WR, Wood JL. Factors associated with failure of thoroughbred horses to train and race. Equine Vet J 2006;38:113-118. (Pubitemid 44440900)
Kohut ML, Davis JM, Jackson DA, Jani P, Ghaffar A, Mayer EP, Essig DA. Exercise effects on IFN-beta expression and viral replication in lung macrophages after HSV-1 infection. Am J Physiol 1998;275:L1089-L1094.
Raidal SL, Rose RJ, Love DN. Effects of training on resting peripheral blood and BAL-derived leucocyte function in horses. Equine Vet J 2001;33:238-243. (Pubitemid 33673105)
Raidal SL, Love DN, Bailey GD, Rose RJ. The effect of high intensity exercise on the functional capacity of equine pulmonary alveolar macrophages and BAL-derived lymphocytes. Res Vet Sci 2000;68:249-253.
Kohut ML, Davis JM, Jackson DA, Colbert LH, Strasner A, Essig DA, Pate RR, Ghaffar A, Mayer EP. The role of stress hormones in exercise-induced suppression of alveolar macrophage antiviral function. J Neuroimmunol 1998;81:193-200. (Pubitemid 28248200)
Chen L, Zhang Z, Barletta KE, Burdick MD, Mehrad B. Heterogeneity of lung mononuclear phagocytes during pneumonia: contribution of chemokine receptors. Am J Physiol Lung Cell Mol Physiol 2013;305:L702-L711.
Goodyear A, Troyer R, Bielefeldt-Ohmann H, Dow S. MyD88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection. Infect Immun 2012;80:110-120.
Horohov DW, Dimock A, Guirnalda P, Folsom RW, McKeever KH, Malinowski K. Effect of exercise on the immune response of young and old horses. Am J Vet Res 1999;60:643-647. (Pubitemid 129532155)
Robson PJ, Alston TD, Myburgh KH. Prolonged suppression of the innate immune system in the horse following an 80 km endurance race. Equine Vet J 2003;35:133-137. (Pubitemid 38698760)
Cywinska A, Szarska E, Degorski A, Guzera M, Gorecka R, Strzelec K, Kowalik S, Schollenberger A, Winnicka A. Blood phagocyte activity after race training sessions in Thoroughbred and Arabian horses. Res Vet Sci 2013;95:459-464.
Bamberger CM, Schulte HM, Chrousos GP. Molecular determinants of glucocorticoid receptor function and tissue sensitivity to glucocorticoids. Endocr Rev 1996;17:245-261. (Pubitemid 26001083)
Jefferies WM. Cortisol and immunity. Med Hypotheses 1991;34:198-208.
Magnuson NS, McGuire TC, Banks KL, Perryman LE. In vitro and in vivo effects of corticosteroids on peripheral blood lymphocytes from ponies. Am J Vet Res 1978;39:393-398. (Pubitemid 10205847)
