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PMID:16601243

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Citation

Blumenthal, A, Ehlers, S, Lauber, J, Buer, J, Lange, C, Goldmann, T, Heine, H, Brandt, E and Reiling, N (2006) The Wingless homolog WNT5A and its receptor Frizzled-5 regulate inflammatory responses of human mononuclear cells induced by microbial stimulation. Blood 108:965-73

Abstract

Microarray--assisted gene--expression screens of human macrophages revealed WNT5A, a homolog of Wingless, a key regulator of Drosophila melanogaster embryonic segmentation and patterning, to be consistently up-regulated following stimulation with different mycobacterial species and conserved bacterial structures. The expression of WNT5A required Toll-like receptor signaling and NF-kappaB activation, which identifies a novel induction pathway for a Wingless homolog. We show that human peripheral-blood mononuclear cells express the WNT5A receptor Frizzled-5 (FZD5). Both WNT5A and FZD5 also were detected in granulomatous lesions in the lungs of Mycobacterium tuberculosis-infected patients. Functional studies showed that WNT5A and FZD5 regulate the microbially induced interleukin-12 response of antigen-presenting cells and interferon-gamma production by mycobacterial antigen-stimulated T cells. Our findings implicate the evolutionarily conserved WNT/Frizzled signaling system in bridging innate and adaptive immunity to infections.

Links

PubMed Online version:10.1182/blood-2005-12-5046

Keywords

Antigen-Presenting Cells/immunology; Antigens, Bacterial/immunology; Frizzled Receptors/physiology; Gene Expression Profiling; Humans; Inflammation/immunology; Macrophages/immunology; Monocytes/immunology; Mycobacterium tuberculosis/immunology; Proto-Oncogene Proteins/genetics; Proto-Oncogene Proteins/physiology; Receptors, G-Protein-Coupled/physiology; Signal Transduction/immunology; Tuberculosis, Pulmonary/immunology; Tuberculosis, Pulmonary/pathology; Up-Regulation/genetics; Wnt Proteins/genetics; Wnt Proteins/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

HUMAN:FZD5

GO:0002726: positive regulation of T cell cytokine production

ECO:0000314:

P

Figure 6

IFN-gamma release of PBMCs was dose-dependently and significantly decreased with increasing concentrations of the anti-FZD5 antiserum

complete
CACAO 6665

HUMAN:FZD5

involved_in

GO:0002726: positive regulation of T cell cytokine production

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD5

involved_in

GO:0071219: cellular response to molecule of bacterial origin

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FZD5

involved_in

GO:0032729: positive regulation of interferon-gamma production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT5A

involved_in

GO:0032729: positive regulation of interferon-gamma production

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:WNT5A

involved_in

GO:0071219: cellular response to molecule of bacterial origin

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:TLR2

involved_in

GO:0030177: positive regulation of Wnt signaling pathway

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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