Blastomyces dermatitidis yeast cells inhibit nitric oxide production by alveolar macrophage inducible nitric oxide

Nicole M Rocco1, John C Carmen, Bruce S Klein

  • 1Microbiology Doctoral Training Program, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA.

Infection and Immunity
|March 30, 2011
PubMed

Insights

Blastomyces dermatitidis yeast cells evade immune cells by suppressing nitric oxide production. This mechanism inhibits macrophage killing, highlighting a potential target for new antifungal drugs.

Area of Science:

  • Mycology
  • Immunology
  • Pathogen Virulence

Background:

  • Pathogen evasion of host defenses is key to virulence.
  • Blastomyces dermatitidis is a fungal pathogen causing pulmonary infections.
  • B. dermatitidis resists alveolar macrophage killing, with mechanisms previously undescribed.

Purpose of the Study:

  • Investigate Blastomyces dermatitidis subversion of macrophage antimicrobial mechanisms.
  • Focus on the role of nitric oxide (NO) in macrophage resistance.
  • Determine how B. dermatitidis interacts with macrophage NO production.

Main Methods:

  • Cultured B. dermatitidis yeast cells and murine alveolar macrophages.
  • Measured nitric oxide levels in macrophage supernatants.
  • Assessed inducible nitric oxide synthase (iNOS) expression and activity.

Main Results:

  • B. dermatitidis yeast cells significantly reduced nitric oxide levels in activated macrophages.
  • This reduction resulted from suppressed NO production, not NO detoxification.
  • Yeast cells did not affect iNOS upregulation or substrate availability, but inhibited iNOS enzymatic activity.

Conclusions:

  • Blastomyces dermatitidis inhibits macrophage nitric oxide production by targeting iNOS enzymatic activity.
  • This suppression of nitric oxide represents a novel virulence mechanism.
  • Understanding this pathway may reveal new antifungal drug targets.

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