Frizzled1 is a marker of inflammatory macrophages, and its ligand Wnt3a is involved in reprogramming Mycobacterium tuberculosis-infected macrophages.
FASEB J
; 24(11): 4599-612, 2010 Nov.
Article
em En
| MEDLINE
| ID: mdl-20667980
ABSTRACT
Wnt/Frizzled signaling, essential for embryonic development, has also recently been implicated in the modulation of inflammatory processes. In the current study, we observed a reciprocal regulation of the Toll-like receptor (TLR)/nuclear factor-κB (NF-κB) and the Wnt/ß-catenin pathway after aerosol infection of mice with Mycobacterium tuberculosis whereas proinflammatory mediators were substantially increased, ß-catenin signaling was significantly reduced. A systematic screen of Fzd homologs in infected mice identified Fzd1 mRNA to be significantly up-regulated during the course of infection. In vitro infection of murine macrophages led to a strong induction of Fzd1 that was dependent on TLRs, the myeloid differentiation response gene 88 (MyD88), and a functional NF-κB pathway. Flow cytometry demonstrated an elevated Fzd1 expression on macrophages in response to M. tuberculosis that was synergistically enhanced in the presence of IFN-γ. Addition of the Fzd1 ligand Wnt3a induced Wnt/ß-catenin signaling in murine macrophages that was inhibited in the presence of a soluble Fzd1/Fc fusion protein. Furthermore, Wnt3a reduced TNF release, suggesting that Wnt3a promotes anti-inflammatory functions in murine macrophages. The current data support the notion that evolutionarily conserved Wnt/Fzd signaling is involved in balancing the inflammatory response to microbial stimulation of innate immune cells of vertebrate origin.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Tuberculose
/
Receptores Acoplados a Proteínas G
/
Proteínas Wnt
/
Receptores Frizzled
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Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Ano de publicação:
2010
Tipo de documento:
Article