TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury
Lung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, for example through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, t...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2020-01-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/50458 |
| _version_ | 1811202669442760704 |
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| author | Salik Hussain Collin G Johnson Joseph Sciurba Xianglin Meng Vandy P Stober Caini Liu Jaime M Cyphert-Daly Katarzyna Bulek Wen Qian Alma Solis Yosuke Sakamachi Carol S Trempus Jim J Aloor Kym M Gowdy W Michael Foster John W Hollingsworth Robert M Tighe Xiaoxia Li Michael B Fessler Stavros Garantziotis |
| author_facet | Salik Hussain Collin G Johnson Joseph Sciurba Xianglin Meng Vandy P Stober Caini Liu Jaime M Cyphert-Daly Katarzyna Bulek Wen Qian Alma Solis Yosuke Sakamachi Carol S Trempus Jim J Aloor Kym M Gowdy W Michael Foster John W Hollingsworth Robert M Tighe Xiaoxia Li Michael B Fessler Stavros Garantziotis |
| author_sort | Salik Hussain |
| collection | DOAJ |
| description | Lung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, for example through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, the prototypic receptor for LPS, also mediates inflammation after O3, triggered by endogenous hyaluronan. Regulation of TLR4 signaling is incompletely understood. TLR5, the flagellin receptor, is expressed in alveolar macrophages, and regulates immune responses to environmental injury. Using in vivo animal models of TLR4-mediated inflammations (LPS, O3, hyaluronan), we show that TLR5 impacts the in vivo response to LPS, hyaluronan and O3. We demonstrate that immune cells of human carriers of a dominant negative TLR5 allele have decreased inflammatory response to O3 exposure ex vivo and LPS exposure in vitro. Using primary murine macrophages, we find that TLR5 physically associates with TLR4 and biases TLR4 signaling towards the MyD88 pathway. Our results suggest an updated paradigm for TLR4/TLR5 signaling. |
| first_indexed | 2024-04-12T02:42:31Z |
| format | Article |
| id | doaj.art-e3dac700dd8e4f4eb86e206a0c3f77fa |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T02:42:31Z |
| publishDate | 2020-01-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-e3dac700dd8e4f4eb86e206a0c3f77fa2022-12-22T03:51:16ZengeLife Sciences Publications LtdeLife2050-084X2020-01-01910.7554/eLife.50458TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injurySalik Hussain0Collin G Johnson1Joseph Sciurba2Xianglin Meng3Vandy P Stober4Caini Liu5Jaime M Cyphert-Daly6Katarzyna Bulek7https://orcid.org/0000-0001-8064-7047Wen Qian8Alma Solis9Yosuke Sakamachi10Carol S Trempus11Jim J Aloor12Kym M Gowdy13W Michael Foster14John W Hollingsworth15Robert M Tighe16Xiaoxia Li17https://orcid.org/0000-0002-4872-9525Michael B Fessler18Stavros Garantziotis19https://orcid.org/0000-0003-4007-375XNational Institute of Environmental Health Sciences, Research Triangle Park, United States; Department of Physiology and Pharmacology, School of Medicine, West Virginia University, Morgantown, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; Center for Cell and Gene Therapy, Baylor College of Medicine, Houston, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; Department of Veterinary Medicine, North Carolina State University, Raleigh, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; Department of ICU, First Affiliated Hospital of Harbin Medical University, Harbin, ChinaNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesLerner Research Institute, Cleveland Clinic Foundation, Cleveland, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; Duke University Medical Center, Durham, United StatesLerner Research Institute, Cleveland Clinic Foundation, Cleveland, United States; Department of Immunology, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Krakow, PolandLerner Research Institute, Cleveland Clinic Foundation, Cleveland, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; East Carolina University Brody School of Medicine, Greenville, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United States; East Carolina University Brody School of Medicine, Greenville, United StatesDuke University Medical Center, Durham, United StatesDuke University Medical Center, Durham, United StatesDuke University Medical Center, Durham, United StatesLerner Research Institute, Cleveland Clinic Foundation, Cleveland, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesNational Institute of Environmental Health Sciences, Research Triangle Park, United StatesLung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, for example through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, the prototypic receptor for LPS, also mediates inflammation after O3, triggered by endogenous hyaluronan. Regulation of TLR4 signaling is incompletely understood. TLR5, the flagellin receptor, is expressed in alveolar macrophages, and regulates immune responses to environmental injury. Using in vivo animal models of TLR4-mediated inflammations (LPS, O3, hyaluronan), we show that TLR5 impacts the in vivo response to LPS, hyaluronan and O3. We demonstrate that immune cells of human carriers of a dominant negative TLR5 allele have decreased inflammatory response to O3 exposure ex vivo and LPS exposure in vitro. Using primary murine macrophages, we find that TLR5 physically associates with TLR4 and biases TLR4 signaling towards the MyD88 pathway. Our results suggest an updated paradigm for TLR4/TLR5 signaling.https://elifesciences.org/articles/50458inflammationinnate immune receptorsTLR4TLR5 |
| spellingShingle | Salik Hussain Collin G Johnson Joseph Sciurba Xianglin Meng Vandy P Stober Caini Liu Jaime M Cyphert-Daly Katarzyna Bulek Wen Qian Alma Solis Yosuke Sakamachi Carol S Trempus Jim J Aloor Kym M Gowdy W Michael Foster John W Hollingsworth Robert M Tighe Xiaoxia Li Michael B Fessler Stavros Garantziotis TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury eLife inflammation innate immune receptors TLR4 TLR5 |
| title | TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury |
| title_full | TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury |
| title_fullStr | TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury |
| title_full_unstemmed | TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury |
| title_short | TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury |
| title_sort | tlr5 participates in the tlr4 receptor complex and promotes myd88 dependent signaling in environmental lung injury |
| topic | inflammation innate immune receptors TLR4 TLR5 |
| url | https://elifesciences.org/articles/50458 |
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