Escherichia coli and TNF-α Modulate Macrophage Phagocytosis of Candida glabrata1

Hess, Donavon J.; Henry-Stanley, Michelle J.; Bendel, Catherine M.; Zhang, Bin; Johnson, Mary-Alice; Wells, Carol L.

doi:10.1016/j.jss.2008.07.022

« Previous Next »Journal of Surgical Research
Volume 155, Issue 2 , Pages 217-224, August 2009

Escherichia coli and TNF-α Modulate Macrophage Phagocytosis of Candida glabrata¹

Donavon J. Hess, M.D., Ph.D.
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
Michelle J. Henry-Stanley, Ph.D.
- Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
Catherine M. Bendel, M.D.
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
Bin Zhang, M.D., Ph.D.
- Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
Mary-Alice Johnson, M.D.
- Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota
Carol L. Wells, Ph.D.
- Department of Surgery, University of Minnesota, Minneapolis, Minnesota
- Department Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, Minnesota
- To whom correspondence and reprint requests should be addressed at the Department of Laboratory Medicine and Pathology, Mayo Mail Code 609, University of Minnesota, Minneapolis

Received 7 January 2008 published online 28 August 2008.

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.

Key Words: Candida glabrata, Escherichia coli, lipopolysaccharide, tumor necrosis factor-α, macrophage