Microbial mannan inhibits bacterial killing by macrophages: a possible pathogenic mechanism for Crohn's disease.
Gastroenterology
; 133(5): 1487-98, 2007 Nov.
Article
en En
| MEDLINE
| ID: mdl-17919633
ABSTRACT
BACKGROUND & AIMS:
Crohn's disease (CD) is mimicked by inherited phagocyte disorders and is associated with circulating antibodies against yeast mannan (anti-Saccharomyces cerevisiae antibody; ASCA). We speculated that mannans might impair phagocyte function.METHODS:
S cerevisiae mannan was assessed for its effects on human peripheral blood neutrophils, adherent monocytes, and monocyte-derived macrophages (MDM).RESULTS:
Mannan caused dose-related increased survival of CD Escherichia coli HM605 within adherent monocytes from 24% +/- 10.5% (control) to 114% +/- 22.7% with mannan 1 mg/mL at 2 hours (mean +/- SEM, n = 9; P = .0002). Electron microscopy showed E coli HM605 surviving and probably replicating within macrophage vesicles. Mannan (1 mg/mL) inhibited the respiratory burst in neutrophils and monocytes (both P = .002) and bacterial killing within MDM (P < .001). E coli survival was increased within macrophages from TLR4(-/-) (126% +/- 3.5% survival at 2 hours) and MyD88(-/-) (134.8% +/- 6.5%) mice compared with wild-type mice (both P < .0001). Mannan had no additional effect, showing that TLR4 and MyD88 are involved in bacterial killing by macrophages and its inhibition by mannan. Putative CD-associated micro-organisms were screened for the ASCA mannan epitope by Galanthus nivalis lectin (GNA) blotting. ASCA epitope was expressed by Candida albicans and Mycobacterium paratuberculosis but not by Mycobacterium tuberculosis or E coli. Supernatants from M paratuberculosis culture inhibited killing of E coli HM605 by adherent human monocytes and murine macrophages. The inhibitory activity was removed by GNA-affinity chromatography.CONCLUSIONS:
Suppression of mucosal phagocyte function by microbial mannans, possibly of Mycobacterial origin, may contribute to CD pathogenesis.
Buscar en Google
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
3_ND
/
4_TD
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
3_neglected_diseases
/
3_tuberculosis
/
3_zoonosis
/
4_tuberculosis
/
6_other_blood_disorders
Asunto principal:
Fagocitosis
/
Saccharomyces cerevisiae
/
Enfermedad de Crohn
/
Macrófagos
/
Mananos
Idioma:
En
Revista:
Gastroenterology
Año:
2007
Tipo del documento:
Article
País de afiliación:
Reino Unido