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Updated: Jun 3, 2026

Assessing Anti-fungal Activity of Isolated Alveolar Macrophages by Confocal Microscopy
Published on: July 9, 2014
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.
Abstract:
The ability of pathogens to evade host antimicrobial mechanisms is crucial to their virulence. The dimorphic fungal pathogen Blastomyces dermatitidis can infect immunocompetent patients, producing a primary pulmonary infection that can later disseminate to other organs. B. dermatitidis possesses a remarkable ability to resist killing by alveolar macrophages. To date, no mechanism to explain this resistance has been described. Here, we focus on macrophage production of the toxic molecule nitric oxide as a potential target of subversion by B. dermatitidis yeast cells. We report that B. dermatitidis yeast cells reduce nitric oxide levels in the supernatants of activated alveolar macrophages. This reduction is not due to detoxification of nitric oxide, but rather to suppression of macrophage nitric oxide production. We show that B. dermatitidis yeast cells do not block upregulation of macrophage inducible nitric oxide synthase (iNOS) expression or limit iNOS access to its arginine substrate. Instead, B. dermatitidis yeast cells appear to inhibit iNOS enzymatic activity. Further investigation into the genetic basis of this potential virulence mechanism could lead to the identification of novel antifungal drug targets.
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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