Document Detail


Respiratory virus-induced TLR7 activation controls IL-17-associated increased mucus via IL-23 regulation.
MedLine Citation:
PMID:  20624950     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Nicholas W Lukacs; Joost J Smit; Sumanta Mukherjee; Susan B Morris; Gabriel Nunez; Dennis M Lindell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-07-12
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  185     ISSN:  1550-6606     ISO Abbreviation:  J. Immunol.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-05     Completed Date:  2010-09-22     Revised Date:  2011-08-16    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2231-9     Citation Subset:  AIM; IM    
Affiliation:
Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. nlukacs@umich.edu
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MeSH Terms
Descriptor/Qualifier:
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:
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:
0/Cytokines; 0/Interleukin-17; 0/Interleukin-23; 0/Membrane Glycoproteins; 0/Tlr7 protein, mouse; 0/Toll-Like Receptor 7
Comments/Corrections

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