Oxidative killing of Cryptococcus neoformans by human neutrophils: Evidence that fungal mannitol protects by scavenging reactive oxygen intermediates

Vishnu Chaturvedi, Brian Wong, Simon L. Newman

Research output: Contribution to journalArticle

132 Scopus citations

Abstract

Polymorphonuclear neutrophils (PMN) kill Cryptococcus neoformans (Cn) by oxidative mechanisms, but the roles of various reactive oxygen intermediates (ROIs) are not known. We used a mannitol low-producing Cn mutant (Cn MLP) and its wild-type parent (Cn H99) to examine the role of ROIs distal to H2O2 in PMN killing and to determine whether mannitol produced by Cn protects the fungus against ROIs. At PMN:Cn cell ratios of 1:1, 10:1, and 100:1, PMN killed significantly more Cn MLP than Cn H99 cells after 2 and 4 h (p < 0.05). Superoxide dismutase and the hydroxyl radical (OH(·)) scavengers mannitol and DMSO inhibited killing of both strains (p < 0.05), but catalase did not. Cn H99 and Cn MLP stimulated PMN to produce similar amounts of O2- and H2O2. In contrast, Cn MLP stimulated greater luminol-dependent chemiluminescence than did Cn H99 (p < 0.05). Finally, H2O2 alone killed similar numbers of Cn H99 and Cn MLP cells, but oxidants generated by FeSO4 (1 μM), H2O2 (10 μM), and iodide (1 to 3 μM) killed significantly more Cn MLP than Cn H99 cells in 1 h (p < 0.05). Mannitol, DMSO, and catalase completely inhibited killing of both Cn strains by this cell free system, but superoxide dismutase did not. These results suggest that 1) distal ROIs such as OH(·) and HOCl are key effector molecules against Cn, and 2) mannitol produced by Cn may protect against oxidative killing by scavenging distal ROIs.

Original languageEnglish (US)
Pages (from-to)3836-3840
Number of pages5
JournalJournal of Immunology
Volume156
Issue number10
StatePublished - May 15 1996

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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