Glycosylation status of the C. albicans cell wall affects the efficiency of neutrophil phagocytosis and killing but not cytokine signaling.

Chirag C Sheth,Leanne Lewis,Lars P Erwig,Rebecca Hall,Neil A R Gow,Alistair J P Brown,Frank C Odds

doi:10.3109/13693786.2010.551425

Abstract

The cell wall of the opportunistic human fungal pathogen, Candida albicans is a complex, layered network of rigid structural polysaccharides composed of β-glucans and chitin that is covered with a fibrillar matrix of highly glycosylated mannoproteins. Poly-morphonuclear cells (PMNs, neutrophils) are the most prevalent circulating phagocytic leukocyte in peripheral blood and they are pivotal in the clearance of invading fungal cells from tissues. The importance of cell-wall mannans for the recognition and uptake of C. albicans by human PMNs was therefore investigated. N- and O-glycosylation-deficient mutants were attenuated in binding and phagocytosis by PMNs and this was associated with reduced killing of C. albicans yeast cells. No differences were found in the production of the respiratory burst enzyme myeloperoxidase (MPO) and the neutrophil chemokine IL-8 in PMNs exposed to control and glycosylation-deficient C. albicans strains. Thus, the significant decrease in killing of glycan-deficient C. albicans strains by PMNs is a consequence of a marked reduction in phagocytosis rather than changes in the release of inflammatory mediators by PMNs.

Highlights

C. albicans is ordinarily found as a commensal yeast colonizing the human gastrointestinal tract
The importance of PMNs in host defense is highlighted in studies showing that neutropenic patients [14,15] and those with peroxidase-deficiency are found to be highly susceptible to invasive C. albicans infections [16,17]
Flow cytometric analysis of attachment and phagocytosis of C. albicans by PMN cells

Summary

Introduction

C. albicans is ordinarily found as a commensal yeast colonizing the human gastrointestinal tract. It is, able to invade and cause deep-seated infections in individuals with compromised host defenses arising from trauma, the administration of immunosuppressive agents, a variety of disease and association with a number of genetic mutations that affect immune recognition [1,2,3]. Contact between pathogen and PMN leads to the further activation of the innate immune system via the production of cytokines and chemotactic factors [11]. Cytokines activate PMNs and other cells in the immediate environment, while chemokine production generates a diffusible leukocyte attraction gradient, drawing increasing numbers of immune cells to the site of infection [12]. The importance of PMNs in host defense is highlighted in studies showing that neutropenic patients [14,15] and those with peroxidase-deficiency are found to be highly susceptible to invasive C. albicans infections [16,17]

Methods

Results

Conclusion