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

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

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Abstract

The cell wall of the opportunistic human fungal pathogen, Candida albicans is a complex, layered network of rigid structural polysaccharides composed of beta beta-glucans and chitin that is covered with a fibrillar matrix of highly glycosylated mannoproteins. Polymorphonuclear 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.</.

Original languageEnglish
Pages (from-to)513-524
Number of pages12
JournalMedical Mycology
Volume49
Issue number5
DOIs
Publication statusPublished - Jul 2011

Keywords

  • C. albicans
  • glycosylation
  • innate immunity
  • PMN
  • pathogen candida-albicans
  • blood-stream infections
  • protein O-mannosylation
  • host-fungus interaction
  • intensive-care-unit
  • N-glycosylation
  • risk-factors
  • beta-glucan
  • polymorphonuclearleukocytes
  • invasive candidiasis

Cite this

Glycosylation status of the C. albicans cell wall affects the efficiency of neutrophil phagocytosis and killing but not cytokine signaling. / Sheth, Chirag C.; Hall, Rebecca; Lewis, Leanne; Brown, Alistair J. P.; Odds, Frank C.; Erwig, Lars P.; Gow, Neil A. R.

In: Medical Mycology, Vol. 49, No. 5, 07.2011, p. 513-524.

Research output: Contribution to journalArticle

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abstract = "The cell wall of the opportunistic human fungal pathogen, Candida albicans is a complex, layered network of rigid structural polysaccharides composed of beta beta-glucans and chitin that is covered with a fibrillar matrix of highly glycosylated mannoproteins. Polymorphonuclear 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.",
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AU - Sheth, Chirag C.

AU - Hall, Rebecca

AU - Lewis, Leanne

AU - Brown, Alistair J. P.

AU - Odds, Frank C.

AU - Erwig, Lars P.

AU - Gow, Neil A. R.

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AB - The cell wall of the opportunistic human fungal pathogen, Candida albicans is a complex, layered network of rigid structural polysaccharides composed of beta beta-glucans and chitin that is covered with a fibrillar matrix of highly glycosylated mannoproteins. Polymorphonuclear 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.

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KW - risk-factors

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