Document Detail


Toll-like receptor 9 enhances nephritogenic immunity and glomerular leukocyte recruitment, exacerbating experimental crescentic glomerulonephritis.
MedLine Citation:
PMID:  20847283     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glomerular disease can be triggered or exacerbated by microbes that activate the immune system by Toll-like receptor (TLR) ligation. TLR9 activation promotes host defenses through the enhancement of innate and adaptive immune responses that facilitate the recruitment of leukocytes to areas of inflammation. We defined the role of TLR9 in experimental crescentic glomerulonephritis. Wild-type mice administered a TLR9 ligand and sheep anti-mouse glomerular basement membrane antibody developed histological injury with impaired renal function, which was attenuated in TLR9 knockout mice. Consistent with enhanced renal injury, wild-type mice exhibited enhanced T helper 1 and T helper 17 cellular immune responses. Kidney mRNA expression of inflammatory cytokines and chemokines as well as leukocyte recruitment were increased in wild-type mice. The use of bone marrow chimeric mice demonstrated that while both bone marrow and tissue cell TLR9 are required for maximal injury, bone marrow TLR9 is more important. Administration of a TLR9 inhibitor before sheep anti-mouse glomerular basement membrane globulin in wild-type mice attenuated cellular nephritogenic immunity that resulted in decreased renal injury. Administration of the inhibitor 7 days after disease initiation decreased glomerular leukocyte recruitment as well as renal injury. These results define the role of TLR9 in experimental crescentic glomerulonephritis and identify therapeutic potential for TLR9 inhibitors in attenuating renal injury, decreasing cellular nephritogenic immunity early in disease, and decreasing kidney effector responses later.
Authors:
Shaun A Summers; Oliver M Steinmetz; Joshua D Ooi; Poh-yi Gan; Kim M O'Sullivan; Kumar Visvanathan; Shizuo Akira; A Richard Kitching; Stephen R Holdsworth
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-16
Journal Detail:
Title:  The American journal of pathology     Volume:  177     ISSN:  1525-2191     ISO Abbreviation:  Am. J. Pathol.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-04     Completed Date:  2011-03-21     Revised Date:  2013-05-27    
Medline Journal Info:
Nlm Unique ID:  0370502     Medline TA:  Am J Pathol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2234-44     Citation Subset:  AIM; IM    
Affiliation:
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Monash Medical Centre, 246 Clayton Rd, Clayton, VIC 3168, Australia.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chemokines / genetics,  immunology
Cytokines / genetics,  immunology
Disease Models, Animal
Glomerulonephritis / immunology*,  pathology,  physiopathology
Leukocytes / immunology*
Mice
Mice, Inbred C57BL
Mice, Knockout
T-Lymphocyte Subsets / immunology
T-Lymphocytes / immunology
Toll-Like Receptor 9 / immunology*
Chemical
Reg. No./Substance:
0/Chemokines; 0/Cytokines; 0/Toll-Like Receptor 9
Comments/Corrections

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