Interactions between Human Bronchoalveolar Macrophages and Blastomyces dermatitidis Conidia: Demonstration of Fungicidal and Fungistatic Effects

Sugar, Alan M.; Picard, Michele; Wagner, Randall P.; Kornfeld, Hardy

doi:10.1093/infdis/171.6.1559

Cited by 19 publications

(9 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, in rat alveolar macrophages, IFN-1' has been demonstrated to suppress phagocytosis and induce the intracellular growth of M. avium complex (21). Sugar and colleagues (22) found that IFN-'Y reduced the capacity of human alveolar macrophages to inhibit phase transition of Blastomyces dermatidis. While the role of IFN-')'…”

Section: Discussionmentioning

confidence: 99%

Interferon-gamma reduces the capacity of human alveolar macrophages to inhibit growth of Cryptococcus neoformans in vitro.

Reardon

Kim²,

Wagner³

et al. 1996

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

Cytokine stimulation of mouse and rat macrophages has previously been shown to enhance their capacity to phagocytose and inhibit the growth of Cryptococcus neoformans. To extend these observations to primary human macrophages, we investigated the anticryptococcal activity of human alveolar macrophages stimulated with interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), or macrophage-colony stimulating factor (M-CSF). Neither TNF-alpha nor M-CSF had any effect on fungal growth inhibition compared with unstimulated macrophages. Alveolar macrophages stimulated with IFN-gamma demonstrated reduced fungistasis for C. neoformans compared with controls (49% +/- 15% versus 75% +/- 12%; mean % growth inhibition +/- SD, P < 0.001). Confocal laser scanning microscopy was used to assess binding and phagocytosis of yeast. No difference was observed between unstimulated macrophages and macrophages stimulated with any of the cytokines tested. These data suggest that the cytokine regulation of anticryptococcal macrophage functions in humans differs from the rat and mouse. Conclusions drawn from these models may not necessarily be applicable to human cryptococcosis. In particular, the effects of IFN-gamma on the interaction of human alveolar macrophages with C. neoformans was not predicted based on the mouse and rat macrophage responses.

show abstract

Section: Discussionmentioning

confidence: 99%

Interferon-gamma reduces the capacity of human alveolar macrophages to inhibit growth of Cryptococcus neoformans in vitro.

Reardon

Kim²,

Wagner³

et al. 1996

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

show abstract

“…In the lung, alveolar macrophages and neutrophils can kill conidia; however, under experimental conditions, not all conidia are killed. 75,76 Conidia that survive the innate immune defenses can germinate as yeast. 55 Yeasts are more difficult to kill by host cells because they inhibit host cell cytokine production, impair CD4 þ T lymphocyte activation, are relatively resistant to reactive oxygen species (ROS), and actively suppress nitric oxide (NO) production.…”

Section: Host Responsementioning

confidence: 99%

New Developments in Blastomycosis

Smith

Gauthier

2015

Semin Respir Crit Care Med

View full text Add to dashboard Cite

Blastomyces dermatitidis, the etiologic agent of blastomycosis, is a thermally dimorphic fungus that grows as a filamentous mold in the environment and as budding yeast in human tissue. This pathogen is endemic to North America, particularly in the states bordering the Mississippi and Ohio rivers, the Great Lakes, and the St. Lawrence Seaway. Infection with B. dermatitidis causes a broad array of clinical manifestations ranging from asymptomatic infection to fulminant sepsis with acute respiratory distress syndrome and death. B. dermatitidis can infect almost any organ in the body, but has a predilection for lungs and skin. There have been recent advances in the understanding of the pathogenesis, diagnosis, and treatment of this fungus. The Infectious Diseases Society of America published updated guidelines in 2008 to guide clinicians in the treatment of this important pathogen.

show abstract

“…The signature Th1 cytokine, IFN-g, manifests pleotropic effects on immune cells during infection. It induces classical activation of macrophages that is critical for arresting growth of intracellular fungal pathogens including H. capsulatum, B. dermatitidis, P. brasiliensis, and Coccidioides immitis (Beaman 1987;Brummer and Stevens 1995;Sugar et al 1995;Calvi et al 2003). These classically activated phagocytes are speculated to mediate their fungicidal activities through the release of nitric oxide and reactive oxygen intermediates ).…”

Section: Th1 Immunitymentioning

confidence: 99%