The iC3b receptor on Candida albicans: subcellular localization and modulation of receptor expression by glucose

M K Hostetter1, J S Lorenz, L Preus

  • 1Department of Pediatrics, University of Minnesota Medical School, Minneapolis.

Insights

Candida albicans expresses a receptor that binds to immune components, with glucose increasing this expression. This enhanced receptor binding on yeast inhibits phagocytosis, explaining why Candida albicans infects patients with high blood sugar.

Area of Science:

  • Mycology
  • Immunology
  • Molecular Biology

Background:

  • Candida albicans, a fungal pathogen, expresses surface receptors for complement fragments like iC3b.
  • These receptors are recognized by antibodies targeting the neutrophil iC3b receptor (CR3).
  • A significant proportion of patients with C. albicans infections are hyperglycemic.

Purpose of the Study:

  • To investigate the effect of glucose on the expression of the C3 fragment iC3b receptor on Candida albicans.
  • To elucidate the mechanism by which hyperglycemia may predispose individuals to C. albicans infections.

Main Methods:

  • Flow cytometry was used to quantify receptor expression on yeast grown in varying glucose concentrations.
  • Phagocytosis assays were performed to assess the impact of glucose-induced receptor expression.
  • SDS-PAGE, Western blotting, and immunodetection were employed to identify the specific protein involved.

Main Results:

  • Yeast grown in D-glucose showed a four- to six-fold increase in iC3b receptor expression compared to yeast grown in L-glutamate.
  • Receptor expression increased proportionally with glucose concentration (0-20 mM).
  • Increased receptor expression due to glucose significantly inhibited yeast phagocytosis.

Conclusions:

  • Glucose significantly upregulates the expression of the iC3b receptor on Candida albicans.
  • This glucose-mediated increase in receptor expression impairs phagocytosis, providing a molecular mechanism for C. albicans' predilection for hyperglycemic hosts.

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