Background: The incidence of systemic nonalbicans Candida (especially C. glabrata) infections is increasing dramatically in intensive care units, but relatively little is known about the pathogenesis or host defenses associated with these life threatening infections. Materials and Methods: The course of systemic C. glabrata infection was assessed as the fungal burden in the kidneys and livers of mice sacrificed 1, 8, and 15 d after intravenous C. glabrata. Sixteen hours before each sacrifice, half of the mice were injected intraperitoneally with intact viable or nonviable E. coli cells, or with E. coli lipopolysaccharide (LPS), or with tumor necrosis factor (TNF)-α. To clarify the effect of LPS and TNF-α on phagocytosis, resident (unstimulated) mouse peritoneal macrophages were harvested, cultivated ex vivo, and some cultures were treated with LPS or TNF-α prior to 30 min incubation with C. glabrata. Results: Compared with mice injected with vehicle, each agent (intact E. coli cells or E. coli LPS or TNF-α) was consistently associated with decreased numbers of tissue C. glabrata, and some of these decreases were significant (P < 0.05). Compared with untreated macrophages, phagocytosis of C. glabrata was increased with LPS-treated macrophages (P < 0.01), and phagocytosis was also increased in the presence of TNF-α (P < 0.01). Conclusion: E. coli LPS and TNF-α may participate in host defense against C. glabrata by a mechanism involving increased macrophage phagocytosis, suggesting that stimulation of inflammatory cytokines may facilitate host clearance of C. glabrata.
|Original language||English (US)|
|Number of pages||8|
|Journal||Journal of Surgical Research|
|State||Published - Aug 2009|
Bibliographical noteFunding Information:
The authors acknowledge support for this work by the United States Public Health Service and National Institutes of Health grant R01 GM059221 and The March of Dimes Birth Defect Foundation grant 6-FY04-53. They acknowledge the excellent technical assistance of Robb Garni, Melody Shepherd, and Milena Sivertson.
- Candida glabrata
- Escherichia coli
- tumor necrosis factor-α