Expression of toll-like receptor 9 in horse lungs.
Abstract: Toll-like receptor 9 (TLR9) has been found to be the main receptor to respond to bacterial DNA in a wide variety of species. Recent work has shown that TLR9 is expressed in a diverse set of cells within the lung. However, much of this data has been centered on human and mouse cell culture lines or primary cultures and very little is known of TLR9 expression in intact lung, especially that of the horse. Here we show that TLR9 is expressed in the lungs of horses in a wide variety of cells. In particular, we note expression in pulmonary intravascular macrophages (PIMs), alveolar macrophages, bronchial epithelial cells, and type-II cells amongst others. Immunogold electron microscopy localized TLR9 in nuclei, cytoplasm, and plasma membrane of various lung cells. The data also show that E. coli lipopolysaccharide significantly increased expression of TLR9 mRNA in lungs and the number of cells in the lung septa that were positive for TLR9 protein. Protein expression was seen in airway epithelium, vascular endothelium, and inflammatory cells in blood vessels. Intravenous administration of gadolinium chloride, which depletes macrophages, before the lipopolysaccharide treatment significantly inhibited the LPS-induced increase in TLR9 mRNA in the lungs of the horses. We conclude that TLR9 is expressed in lung cells including PIMs and that the lipopolysaccharide treatment increases TLR9 mRNA expression. The increase in TLR9 mRNA is eliminated by depletion of PIMs, implicating these cells as a major source of TLR9 in the equine lung.
Publication Date: 2009-06-24 PubMed ID: 19548205DOI: 10.1002/ar.20927Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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This study investigates the presence of Toll-like receptor 9 (TLR9) in horse lungs and its role in responding to bacterial DNA. The results demonstrate TLR9 expression in various lung cells and indicate that certain treatments can increase TLR9 mRNA expression, specifically implicating pulmonary intravascular macrophages.
Understanding TLR9 and Its Role
- TLR9 is identified as the main triggering receptor for bacterial DNA across various species. It is majorly present and active within cells of the lungs.
- However, most of the studies that have generated this data focus on human and mouse cell culture lines. The understanding of TLR9 expression within the structures of intact lungs, and especially in horses, is limited.
TLR9 Expression in Horse Lungs
- The research discovered that TLR9 is indeed expressed in the lungs of horses. It is present in an array of cell types, such as pulmonary intravascular macrophages (PIMs), alveolar macrophages, bronchial epithelial cells, and type-II cells amongst others.
- Through the use of immunogold electron microscopy, TLR9 was found in different components of the lung cells like the nuclei, cytoplasm, and plasma membrane.
Effects of Lipopolysaccharide Treatment on TLR9 Expression
- The study also demonstrated that the treatment of horse lungs with E. coli lipopolysaccharide notably enhanced the expression of TLR9 mRNA and the number of TLR9 protein-positive cells in the lung septa.
- TLR9 protein expression was observed in the airway epithelium (the lining of the airways), vascular endothelium (the innermost layer of blood vessels), and in inflammatory cells within blood vessels.
Role of Macrophages in TLR9 mRNA Expression
- Intravenous administration of gadolinium chloride, a compound that eliminates macrophages before the lipopolysaccharide treatment, significantly suppressed the increase in TLR9 mRNA in the lungs.
- This reveals that pulmonary intravascular macrophages (PIMs) play a critical role in TLR9 mRNA expression, thus being a major source of TLR9 in horse lungs.
In conclusion, TLR9 is actively expressed in horse lung cells, including PIMs. The triggering of these cells appears to heighten TLR9 mRNA expression. Understanding this mechanism holds potential for developing future treatments for lung-associated diseases by targeting TLR9 receptors.
Cite This Article
APA
Schneberger D, Caldwell S, Suri SS, Singh B.
(2009).
Expression of toll-like receptor 9 in horse lungs.
Anat Rec (Hoboken), 292(7), 1068-1077.
https://doi.org/10.1002/ar.20927 Publication
Researcher Affiliations
- Department of Veterinary Biomedical Sciences, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
MeSH Terms
- Animals
- Anti-Inflammatory Agents / pharmacology
- Bronchi / immunology
- Bronchi / metabolism
- Bronchi / ultrastructure
- Endothelial Cells / drug effects
- Endothelial Cells / metabolism
- Gadolinium / pharmacology
- Horses / anatomy & histology
- Horses / metabolism
- Inflammation Mediators
- Lipopolysaccharides / pharmacology
- Lung / immunology
- Lung / metabolism
- Lung / ultrastructure
- Macrophages / drug effects
- Macrophages / metabolism
- Macrophages / ultrastructure
- Microscopy, Immunoelectron
- Pneumonia / immunology
- Pneumonia / metabolism
- Pneumonia / physiopathology
- Pulmonary Artery / drug effects
- Pulmonary Artery / metabolism
- Pulmonary Artery / ultrastructure
- RNA, Messenger / drug effects
- RNA, Messenger / metabolism
- Respiratory Mucosa / metabolism
- Respiratory Mucosa / ultrastructure
- Toll-Like Receptor 9 / genetics
- Toll-Like Receptor 9 / metabolism
- Up-Regulation / drug effects
- Up-Regulation / immunology
Citations
This article has been cited 17 times.- Klier J, Fuchs S, Winter G, Gehlen H. Inhalative Nanoparticulate CpG Immunotherapy in Severe Equine Asthma: An Innovative Therapeutic Concept and Potential Animal Model for Human Asthma Treatment. Animals (Basel) 2022 Aug 16;12(16).
- Arora S, Ahmad S, Irshad R, Goyal Y, Rafat S, Siddiqui N, Dev K, Husain M, Ali S, Mohan A, Syed MA. TLRs in pulmonary diseases. Life Sci 2019 Sep 15;233:116671.
- Klier J, Bartl C, Geuder S, Geh KJ, Reese S, Goehring LS, Winter G, Gehlen H. Immunomodulatory asthma therapy in the equine animal model: A dose-response study and evaluation of a long-term effect. Immun Inflamm Dis 2019 Sep;7(3):130-149.
- Bond S, Léguillette R, Richard EA, Couetil L, Lavoie JP, Martin JG, Pirie RS. Equine asthma: Integrative biologic relevance of a recently proposed nomenclature. J Vet Intern Med 2018 Nov;32(6):2088-2098.
- Klier J, Geis S, Steuer J, Geh K, Reese S, Fuchs S, Mueller RS, Winter G, Gehlen H. A comparison of nanoparticullate CpG immunotherapy with and without allergens in spontaneously equine asthma-affected horses, an animal model. Immun Inflamm Dis 2018 Mar;6(1):81-96.
- Ma L, Yang J, Yang L, Shi J, Xue J, Li Y, Liu X. Developmental expression of Toll‑like receptors in the guinea pig lung. Mol Med Rep 2017 Mar;15(3):1243-1251.
- Kaur S, Mukhopadhyay CS, Sethi RS. Chronic exposure to indoxacarb and pulmonary expression of toll-like receptor-9 in mice. Vet World 2016 Nov;9(11):1282-1286.
- 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.
- Schneberger D, Aulakh G, Channabasappa S, Singh B. Toll-like receptor 9 partially regulates lung inflammation induced following exposure to chicken barn air. J Occup Med Toxicol 2016;11:31.
- Harrison JM, Quanstrom LM, Robinson AR, Wobeser B, Anderson SL, Singh B. Expression of von Willebrand factor, pulmonary intravascular macrophages, and Toll-like receptors in lungs of septic foals. J Vet Sci 2017 Mar 30;18(1):17-23.
- Klier J, Lehmann B, Fuchs S, Reese S, Hirschmann A, Coester C, Winter G, Gehlen H. Nanoparticulate CpG immunotherapy in RAO-affected horses: phase I and IIa study. J Vet Intern Med 2015 Jan;29(1):286-93.
- Schneberger D, Caldwell S, Kanthan R, Singh B. Expression of Toll-like receptor 9 in mouse and human lungs. J Anat 2013 May;222(5):495-503.
- Werners AH, Bryant CE. Pattern recognition receptors in equine endotoxaemia and sepsis. Equine Vet J 2012 Jul;44(4):490-8.
- Lewis DH, Chan DL, Pinheiro D, Armitage-Chan E, Garden OA. The immunopathology of sepsis: pathogen recognition, systemic inflammation, the compensatory anti-inflammatory response, and regulatory T cells. J Vet Intern Med 2012 May-Jun;26(3):457-82.
- Schneberger D, Lewis D, Caldwell S, Singh B. Expression of toll-like receptor 9 in lungs of pigs, dogs and cattle. Int J Exp Pathol 2011 Feb;92(1):1-7.
- Aharonson-Raz K, Singh B. Pulmonary intravascular macrophages and endotoxin-induced pulmonary pathophysiology in horses. Can J Vet Res 2010 Jan;74(1):45-9.
- Rodrigues CR, Aulakh GK, Kroeker A, Kulkarni SS, Lew J, Falzarano D, Singh B. Recruitment of pulmonary intravascular macrophages in SARS-CoV-2 infected hamsters. Cell Tissue Res 2025 Apr;400(1):1-15.
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