Title:
|
Microbial Mannan As A Cause Of Phagocyte Dysfunction In Crohn's Disease
|
Crohn's disease (CD) is a granulomatous condition that is mimicked by rare
inherited disorders of phagocyte function and has clinical features compatible with
an underlying impaired' defence against the gut microbiota. Crohn's'disease patients
commonly have circulating antibodies (ASCA) against a mannan present in baker's
yeast (Saccharomyces cerevisiae). I have investigated the possibility that S.cerevisiae
mam?-ans may induce defects in phagocyte function.
Saccharomyces cerevisiae mannan is shown to inhibit several of the functions
of normal human peripheral blood neutrophils, monocytes and monocyte-derived
macrophages including chemiluminescence and killing of phagocytosed bacteria. CD
mucosa-associated E. coli isolates, that are less readily killed following
internalization within adherent monocytes than a control ATCC259222 E. coli strain,
undergo net replication inside adherent monocytes in the presence of S.cerevisiae
mannan. S.cerevisiae mannan similarly enhanced survival of S. aureus within
adherent monocytes.
The epitope for ASCA is a mannose al-3 mannose disaccharide that binds
snowdrop (Galanthus nivalis) lectin (GNA). A range of putative Crohn's diseaseassociated
organisms was screened by GNA lectin blotting. The ASCA epitope was
expressed by Mycobacterium avium paratuberculosis but not by M tuberculosis or E.
coli.
Crohn's disease may arise in part as a consequence of the suppression of
mucosal phagocyte function by shed microbial mannans.
|