| Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation. | |
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MedLine Citation:
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PMID: 20624950 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The response to respiratory syncytial virus (RSV), negative strand ssRNA virus, depends upon the ability to recognize specific pathogen-associated targets. In the current study, the role of TLR7 that recognizes ssRNA was examined. Using TLR7(-/-) mice, we found that the response to RSV infection in the lung was more pathogenic as assessed by significant increases in inflammation and mucus production. Although there appeared to be no effect of TLR7 deficiency on type I IFN, the pathology was associated with an alteration in T cell responses with increases in mucogenic cytokines IL-4, IL-13, and IL-17. Examination of dendritic cells from TLR7(-/-) animals indicated a preferential activation of IL-23 (a Th17-promoting cytokine) and a decrease in IL-12 production. Neutralization of IL-17 in the TLR7(-/-) mice resulted in a significant decrease in the mucogenic response in the lungs of the RSV-infected mice. Thus, without TLR7-mediated responses, an altered immune environment ensued with a significant effect on airway epithelial cell remodeling and goblet cell hyper/metaplasia, leading to increased mucus production. |
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Authors:
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Nicholas W Lukacs; Joost J Smit; Sumanta Mukherjee; Susan B Morris; Gabriel Nunez; Dennis M Lindell |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2010-07-12 |
Journal Detail:
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Title: Journal of immunology (Baltimore, Md. : 1950) Volume: 185 ISSN: 1550-6606 ISO Abbreviation: J. Immunol. Publication Date: 2010 Aug |
Date Detail:
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Created Date: 2010-08-05 Completed Date: 2010-09-22 Revised Date: 2011-08-16 |
Medline Journal Info:
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Nlm Unique ID: 2985117R Medline TA: J Immunol Country: United States |
Other Details:
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Languages: eng Pagination: 2231-9 Citation Subset: AIM; IM |
Affiliation:
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Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. nlukacs@umich.edu |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cytokines / metabolism Dendritic Cells / immunology, metabolism Flow Cytometry Goblet Cells / immunology, metabolism, pathology Hyperplasia Interleukin-17 / immunology*, metabolism Interleukin-23 / immunology*, metabolism Leukocytes / immunology, metabolism, pathology Lung / immunology, metabolism, virology Membrane Glycoproteins / genetics, immunology*, metabolism Mice Mice, Inbred Strains Mice, Knockout Mucus / metabolism* Respiratory Syncytial Virus Infections / immunology*, metabolism, virology Respiratory Syncytial Viruses / immunology Reverse Transcriptase Polymerase Chain Reaction Toll-Like Receptor 7 / genetics, immunology*, metabolism |
| Grant Support | |
ID/Acronym/Agency:
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K22 AI077712-02/AI/NIAID NIH HHS; R01 AI073876-04/AI/NIAID NIH HHS; R01AI036302/AI/NIAID NIH HHS; R01AI073876/AI/NIAID NIH HHS; T32HL07749/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cytokines; 0/Interleukin-17; 0/Interleukin-23; 0/Membrane Glycoproteins; 0/Tlr7 protein, mouse; 0/Toll-Like Receptor 7 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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