Abstract
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.
MeSH terms
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Adult
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Animals
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Antigens, Helminth / pharmacology
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B-Lymphocytes / immunology
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B-Lymphocytes / metabolism
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B-Lymphocytes / parasitology
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Brugia malayi / immunology
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD4-Positive T-Lymphocytes / parasitology
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Cells, Cultured
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / biosynthesis
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DNA-Binding Proteins / metabolism
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Elephantiasis, Filarial / immunology*
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Elephantiasis, Filarial / metabolism*
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Elephantiasis, Filarial / parasitology
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Female
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Humans
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Interferon-gamma / antagonists & inhibitors
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Interferon-gamma / biosynthesis
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Interleukin-5 / antagonists & inhibitors
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Interleukin-5 / biosynthesis
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Lymphocyte Activation / immunology
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Male
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Membrane Glycoproteins / antagonists & inhibitors*
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology
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Middle Aged
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Monocytes / immunology
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Monocytes / metabolism
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Monocytes / parasitology
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Receptors, Cell Surface / antagonists & inhibitors*
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Receptors, Cell Surface / biosynthesis*
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Receptors, Cell Surface / metabolism
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Receptors, Cell Surface / physiology
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Toll-Like Receptor 1
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptor 9
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Toll-Like Receptors
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Tuberculin / pharmacology
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Wuchereria bancrofti / immunology
Substances
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Antigens, Helminth
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DNA-Binding Proteins
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Interleukin-5
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Membrane Glycoproteins
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Receptors, Cell Surface
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TLR2 protein, human
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TLR4 protein, human
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TLR9 protein, human
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Toll-Like Receptor 1
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Toll-Like Receptor 2
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Toll-Like Receptor 4
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Toll-Like Receptor 9
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Toll-Like Receptors
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Tuberculin
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Interferon-gamma