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Microbial mannan inhibits bacterial killing by macrophages: a possible pathogenic mechanism for Crohn's disease

Chiedzo M Mpofu1, Barry J Campbell, Sreedhar Subramanian

  • 1Division of Gastroenterology, School of Clinical Science, University of Liverpool, Liverpool, United Kingdom.

Gastroenterology
|October 9, 2007
PubMed
Abstract

Insights

Microbial mannans, like those from Mycobacterium, may impair phagocyte function, potentially contributing to Crohn's disease (CD) pathogenesis. This study shows mannans inhibit bacterial killing by immune cells, suggesting a link to CD.

Area of Science:

  • Immunology
  • Microbiology
  • Gastroenterology

Background:

  • Crohn's disease (CD) shares features with inherited phagocyte disorders.
  • Circulating antibodies against yeast mannan (ASCA) are linked to CD.
  • Mannans may impair phagocyte function, a hypothesis explored in this study.

Purpose of the Study:

  • To investigate the effects of Saccharomyces cerevisiae mannan on human phagocyte function.
  • To determine if microbial mannans contribute to Crohn's disease pathogenesis.

Main Methods:

  • Assessed effects of S. cerevisiae mannan on human neutrophils, monocytes, and macrophages.
  • Utilized electron microscopy to observe bacterial survival within macrophages.
  • Screened microorganisms for the ASCA mannan epitope using GNA blotting.
  • Investigated the role of TLR4 and MyD88 in macrophage bacterial killing.

Main Results:

  • Mannan significantly increased Escherichia coli survival within human monocytes and inhibited neutrophil and monocyte respiratory burst.
  • Mannan impaired bacterial killing in human monocyte-derived macrophages.
  • TLR4 and MyD88 pathways are involved in macrophage bacterial killing and its inhibition by mannan.
  • The ASCA mannan epitope was found on Candida albicans and Mycobacterium paratuberculosis, but not M. tuberculosis or E. coli.
  • Mycobacterium paratuberculosis culture supernatants inhibited bacterial killing by human and murine macrophages.

Conclusions:

  • Suppression of mucosal phagocyte function by microbial mannans, potentially from Mycobacteria, may contribute to Crohn's disease pathogenesis.
  • These findings suggest a novel mechanism linking microbial components to inflammatory bowel disease.

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