Different susceptibilities of yeasts and conidia of Penicillium marneffei to nitric oxide (NO)-mediated fungicidal activity of murine macrophages

N. Kudeken, K. Kawakami, A. Saito

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Penicillium marneffei is an important opportunistic fungal pathogen. Host defence mechanisms against P. marneffei are not fully understood. We investigated the fungicidal activity of murine peritoneal macrophages against two forms of P. marneffei, conidia and yeast cells, and the involvement of the NO-mediated killing system. Peritoneal macrophages suppressed the intracellular growth of P. marneffei yeast cells and conidia. The number of live yeast cells within macrophages was significantly reduced by activation of macrophages by interferon-gamma (IFN-γ), while a similar response was not observed with conidia. IFN-γ-induced macrophage fungicidal activity against yeast cells was mediated by NO and was almost completely inhibited by N(G)- monomethyl-L-arginine (L-NMMA), a competitive inhibitor of NO synthesis, while N(G)-monomethyl-D-arginine (D-NMMA), an optical isomer of L-NMMA, did not show any influence. NO production by macrophages stimulated with IFN-γ was significantly enhanced when these macrophages were cultured with P. marneffei yeast cells, while conidia did not enhance macrophage NO production. Furthermore, yeast cells were more susceptible to the killing effect of chemically generated NO than conidia. Our results indicate that the yeast form of P. marneffei is more sensitive to the fungicidal activity of IFN-γ-stimulated macrophages than conidia, and suggest that the different effects of two forms of P. marneffei on macrophage NO production and their different susceptibilities to NO may be reasons for the present findings.

Original languageEnglish
Pages (from-to)287-293
Number of pages7
JournalClinical and Experimental Immunology
Volume112
Issue number2
DOIs
Publication statusPublished - 1998
Externally publishedYes

Keywords

  • Conidia
  • Macrophages
  • Nitric oxide
  • Penicillium marneffei
  • Yeast

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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