Tamm-Horsfall glycoprotein links innate immune cell activation with adaptive immunity via a Toll-like receptor-4-dependent mechanism.
J Clin Invest
; 115(2): 468-75, 2005 Feb.
Article
em En
| MEDLINE
| ID: mdl-15650774
ABSTRACT
Tamm-Horsfall glycoprotein (THP) is expressed exclusively in the kidney and constitutes the most abundant protein in mammalian urine. A critical role for THP in antibacterial host defense and inflammatory disorders of the urogenital tract has been suggested. We demonstrate that THP activates myeloid DCs via Toll-like receptor-4 (TLR4) to acquire a fully mature DC phenotype. THP triggers typical TLR signaling, culminating in activation of NF-kappaB. Bone marrow-derived macrophages from TLR4- and MyD88-deficient mice were nonresponsive to THP in contrast to those from TLR2- and TLR9-deficient mice. In vivo THP-driven TNF-alpha production was evident in WT but not in Tlr4-/- mice. Importantly, generation of THP-specific Abs consistently detectable in urinary tract inflammation was completely blunted in Tlr4-/- mice. These data show that THP is a regulatory factor of innate and adaptive immunity and therefore could have significant impact on host immunity in the urinary tract.
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Base de dados:
MEDLINE
Assunto principal:
Infecções Urinárias
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Células Dendríticas
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Transdução de Sinais
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Receptores de Superfície Celular
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Imunidade Inata
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Mucoproteínas
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article