Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages.
Abstract: In humans, strenuous exercise causes increased susceptibility to respiratory infections associated with down-regulated expression of Toll-like receptors (TLRs) and costimulatory and antigen-presenting molecules. Lower airway diseases are also a common problem in sport and racing horses. Because innate immunity plays an essential role in lung defense mechanisms, we assessed the effect of acute exercise and training on innate immune responses in two different compartments. Blood monocytes and pulmonary alveolar macrophages (PAMs) were collected from horses in untrained, moderately trained, intensively trained, and deconditioned states before and after a strenuous exercise test. The cells were analyzed for TLR messenger ribonucleic acid (mRNA) expression by real-time PCR in vitro, and 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 LPS and a synthetic diacylated lipoprotein showed increased cytokine secretion in trained and deconditioned subjects, indicating the activation of cells at the systemic level. The production of TNF-α and IFN-β in nonstimulated and stimulated PAMs 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.
Publication Date: 2014-02-08 PubMed ID: 24502337DOI: 10.1165/rcmb.2013-0341OCGoogle Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study showcases how physical training, not just strenuous exercise, affects the innate immune responses in two different compartments of humans and horses – the blood monocytes and pulmonary alveolar macrophages (PAMs). Notably, it was observed that training affects the expression of toll-like receptors (TLRs) which play key roles in lung defense mechanisms, ultimately modifying susceptibility to respiratory infections.
Methodology and Data Collection
- The researchers collected blood monocytes and pulmonary alveolar macrophages (PAMs) from untrained, moderately trained, intensively trained, and deconditioned horses before and after a strenuous exercise test. This was done to examine the effect of varying stages of physical conditioning on innate immune responses.
- TLR mRNA expression was analyzed in vitro using real-time PCR to measure the alterations in expression that occurred due to training.
- Cytokine production, an important factor in inflammatory and immune responses, was observed after in vitro stimulation with TLR ligands, a process which is measured through ELISA (Enzyme-Linked Immunosorbent Assay).
Discussion of the Results
- The results demonstrated that training, as opposed to acute exercise, modified the innate immune responses in both cell types.
- Training down-regulated the mRNA expression of TLR3 in both cell types while up-regulating the expression of TLR4 in monocytes, implying an alteration in the immune response due to physical conditioning.
- Increased cytokine secretion was observed in trained and deconditioned subjects once monocytes were treated with LPS (a bacterial endotoxin) and a synthetic diacylated lipoprotein. This suggests a heightened activation of cells at the systemic level in response to these treatments.
- The production of TNF-α (tumor necrosis factor alpha) and IFN-β (interferon beta), which plays crucial roles in the immune response, decreased in non-stimulated and stimulated PAMs in trained and deconditioned horses.
- The observed decrease in the production of these immune response regulators could explain the increased susceptibility to respiratory infections, linking physical training with immune response alteration.
Conclusion of the Study
- This research provides evidence of a dissociation between the systemic level and lung response to training and physical conditioning.
- Such dissociation is likely implicated in systemic inflammation as well as an increased susceptibility to pulmonary infections, providing a link between physical exercise, training, and immune response.
Cite This Article
APA
Frellstedt L, Waldschmidt I, Gosset P, Desmet C, Pirottin D, Bureau F, Farnir F, Franck T, Dupuis-Tricaud MC, Lekeux P, Art T.
(2014).
Training modifies innate immune responses in blood monocytes and in pulmonary alveolar macrophages.
Am J Respir Cell Mol Biol, 51(1), 135-142.
https://doi.org/10.1165/rcmb.2013-0341OC Publication
Researcher Affiliations
- 1 Center of Equine Sports Medicine, University of Liege, Liege, Belgium.
MeSH Terms
- Animals
- Blotting, Western
- Female
- Horses
- Hydrocortisone / metabolism
- Immunity, Innate / immunology
- Inflammation / immunology
- Inflammation / metabolism
- Inflammation / pathology
- Interferon-beta / genetics
- Interferon-beta / metabolism
- Longitudinal Studies
- Lung / immunology
- Lung / metabolism
- Macrophages, Alveolar / immunology
- Macrophages, Alveolar / metabolism
- Monocytes / immunology
- Monocytes / metabolism
- Physical Conditioning, Animal
- RNA, Messenger / genetics
- Real-Time Polymerase Chain Reaction
- Reverse Transcriptase Polymerase Chain Reaction
- Toll-Like Receptors / metabolism
- Tumor Necrosis Factor-alpha / genetics
- Tumor Necrosis Factor-alpha / metabolism
Citations
This article has been cited 13 times.- Zandoná Meleiro MC, de Carvalho HJC, Ribeiro RR, da Silva MD, Salles Gomes CM, Miglino MA, de Santis Prada IL. Immune Functions Alterations Due to Racing Stress in Thoroughbred Horses. Animals (Basel) 2022 May 7;12(9).
- Karagianni AE, Kurian D, Cillán-Garcia E, Eaton SL, Wishart TM, Pirie RS. Training associated alterations in equine respiratory immunity using a multiomics comparative approach. Sci Rep 2022 Jan 10;12(1):427.
- Picetti TS, Soveral LF, Miotto R, Erpen LMS, Kreutz Y, Guizzo JA, Frandoloso R, Kreutz LC. Orally administered β-glucan improves the hemolytic activity of the complement system in horses. Vet World 2021 Apr;14(4):835-840.
- Witkowska-Piłaszewicz O, Pingwara R, Szczepaniak J, Winnicka A. The Effect of the Clenbuterol-β2-Adrenergic Receptor Agonist on the Peripheral Blood Mononuclear Cells Proliferation, Phenotype, Functions, and Reactive Oxygen Species Production in Race Horses In Vitro. Cells 2021 Apr 17;10(4).
- Zhou J, Lv J, Carlson C, Liu H, Wang H, Xu T, Wu F, Song C, Wang X, Wang T, Qian Z. Trained immunity contributes to the prevention of Mycobacterium tuberculosis infection, a novel role of autophagy. Emerg Microbes Infect 2021 Dec;10(1):578-588.
- Witkowska-Piłaszewicz O, Pingwara R, Winnicka A. The Effect of Physical Training on Peripheral Blood Mononuclear Cell Ex Vivo Proliferation, Differentiation, Activity, and Reactive Oxygen Species Production in Racehorses. Antioxidants (Basel) 2020 Nov 20;9(11).
- Adams K, Weber KS, Johnson SM. Exposome and Immunity Training: How Pathogen Exposure Order Influences Innate Immune Cell Lineage Commitment and Function. Int J Mol Sci 2020 Nov 11;21(22).
- Nieman DC. Coronavirus disease-2019: A tocsin to our aging, unfit, corpulent, and immunodeficient society. J Sport Health Sci 2020 Jul;9(4):293-301.
- Pollán M, Casla-Barrio S, Alfaro J, Esteban C, Segui-Palmer MA, Lucia A, Martín M. Exercise and cancer: a position statement from the Spanish Society of Medical Oncology. Clin Transl Oncol 2020 Oct;22(10):1710-1729.
- Sloan RP, Shapiro PA, McKinley PS, Bartels M, Shimbo D, Lauriola V, Karmally W, Pavlicova M, Choi CJ, Choo TH, Scodes JM, Flood P, Tracey KJ. Aerobic Exercise Training and Inducible Inflammation: Results of a Randomized Controlled Trial in Healthy, Young Adults. J Am Heart Assoc 2018 Sep 4;7(17):e010201.
- Rusek P, Wala M, Druszczyńska M, Fol M. Infectious Agents as Stimuli of Trained Innate Immunity. Int J Mol Sci 2018 Feb 3;19(2).
- Tarlinton RE, Alder L, Moreton J, Maboni G, Emes RD, Tötemeyer S. RNA expression of TLR10 in normal equine tissues. BMC Res Notes 2016 Jul 19;9:353.
- Frellstedt L, Gosset P, Kervoaze G, Hans A, Desmet C, Pirottin D, Bureau F, Lekeux P, Art T. The innate immune response of equine bronchial epithelial cells is altered by training. Vet Res 2015 Jan 17;46(1):3.
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