Document Detail


Diminished expression and function of TLR in lymphatic filariasis: a novel mechanism of immune dysregulation.
MedLine Citation:
PMID:  16002719     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lymphatic filariasis is a disease characterized by immune dysregulation involving APC and T cell populations. To assess the contribution of TLR in mediating this dysregulation, we examined the expression of TLR1, TLR2, TLR4, and TLR9 on B cells and monocytes of filaria-infected and uninfected individuals. Baseline expression of TLR was significantly lower in B cells but not in monocytes of the filaria-infected group compared with the uninfected group. Upon stimulation with filarial Ag, a diminished up-regulation of TLR was observed in both B cells and monocytes of infected individuals. Finally, stimulation of B cells and monocytes with TLR ligands resulted in decreased B cell and monocyte activation/cytokine production, indicating a state of immune tolerance. This dysregulation is associated with diminished CD4(+) T cell production of IFN-gamma and IL-5. The diminished expression and function of TLR is thus a likely consequence of chronic Ag stimulation and could serve as a novel mechanism underlying the dysfunctional immune response in filariasis.
Authors:
Subash Babu; Carla P Blauvelt; V Kumaraswami; Thomas B Nutman
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Publication Detail:
Type:  Comparative Study; Journal Article    
Journal Detail:
Title:  Journal of immunology (Baltimore, Md. : 1950)     Volume:  175     ISSN:  0022-1767     ISO Abbreviation:  J. Immunol.     Publication Date:  2005 Jul 
Date Detail:
Created Date:  2005-07-08     Completed Date:  2005-09-27     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  2985117R     Medline TA:  J Immunol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1170-6     Citation Subset:  AIM; IM    
Affiliation:
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 4 Center Drive, Bethesda, MD 20892, USA. sbabu@niaid.nih.gov
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MeSH Terms
Descriptor/Qualifier:
Adult
Animals
Antigens, Helminth / pharmacology
B-Lymphocytes / immunology,  metabolism,  parasitology
Brugia malayi / immunology
CD4-Positive T-Lymphocytes / immunology,  metabolism,  parasitology
Cells, Cultured
DNA-Binding Proteins / antagonists & inhibitors,  biosynthesis,  metabolism
Elephantiasis, Filarial / immunology*,  metabolism*,  parasitology
Female
Humans
Interferon-gamma / antagonists & inhibitors,  biosynthesis
Interleukin-5 / antagonists & inhibitors,  biosynthesis
Lymphocyte Activation / immunology
Male
Membrane Glycoproteins / antagonists & inhibitors*,  biosynthesis*,  metabolism,  physiology
Middle Aged
Monocytes / immunology,  metabolism,  parasitology
Receptors, Cell Surface / antagonists & inhibitors*,  biosynthesis*,  metabolism,  physiology
Toll-Like Receptor 1
Toll-Like Receptor 2
Toll-Like Receptor 4
Toll-Like Receptor 9
Toll-Like Receptors
Tuberculin / pharmacology
Wuchereria bancrofti / immunology
Chemical
Reg. No./Substance:
0/Antigens, Helminth; 0/DNA-Binding Proteins; 0/Interleukin-5; 0/Membrane Glycoproteins; 0/Receptors, Cell Surface; 0/TLR2 protein, human; 0/TLR4 protein, human; 0/TLR9 protein, human; 0/Toll-Like Receptor 1; 0/Toll-Like Receptor 2; 0/Toll-Like Receptor 4; 0/Toll-Like Receptor 9; 0/Toll-Like Receptors; 0/Tuberculin; 82115-62-6/Interferon-gamma

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