Escherichia coli and TNF-alpha modulate macrophage phagocytosis of Candida glabrata.
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.


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)-alpha. To clarify the effect of LPS and TNF-alpha on phagocytosis, resident (unstimulated) mouse peritoneal macrophages were harvested, cultivated ex vivo, and some cultures were treated with LPS or TNF-alpha 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-alpha) 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-alpha (P < 0.01).


CONCLUSIONS
E. coli LPS and TNF-alpha 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.
Hess
Donavon J
DJ
Department of Surgery, University of Minnesota, Minneapolis, Minnesota, USA.
Henry-Stanley
Michelle J
MJ
Bendel
Catherine M
CM
Zhang
Bin
B
Johnson
Mary-Alice
MA
Wells
Carol L
CL
D000818:Animals; D041221:Candida glabrata / Q000502:physiology*; D002177:Candidiasis / Q000517:prevention & control; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004926:Escherichia coli / Q000502:physiology*; D005260:Female; D007668:Kidney / Q000382:microbiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000382:microbiology; D017737:Macrophages, Peritoneal / Q000166:cytology / Q000502:physiology*; D051379:Mice; D010587:Phagocytosis / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha