BASIC-ALIMENTARY TRACT Microbial Mannan Inhibits Bacterial Killing by Macrophages: A Possible Pathogenic Mechanism for Crohn's Disease
Le résumé fourni par la source
Background & Aims: Crohn’s disease (CD) is mimicked by inherited phagocyte disorders and is associated with circulating antibodies against yeast mannan (antiSaccharomyces 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 wildtype 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 byGalanthus 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.
Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.