Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis

Tammy R Ozment-Skelton, Elizabeth A deFluiter, Tuanzhu Ha, Chan Li, Bridget M Graves, Donald A. Ferguson, John B Schweitzer, Johanna Preizsner, Gordon D Brown, Siamon Gordon, John H Kalbfleisch, David L Williams

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

OBJECTIVE: To examine peripheral leukocyte Dectin-1 regulation in clinically relevant models of fungal and polymicrobial sepsis. DESIGN: Prospective animal study. SETTING: University medical school research laboratory. SUBJECTS: Age, weight, and sex matched ICR/HSD mice. INTERVENTIONS: Mice were infected with Candida albicans (1 x 10, intravenously) or were subjected to cecal ligation and puncture to induce polymicrobial sepsis. MEASUREMENTS: Blood, spleen, and peritoneal exudate were harvested and leukocytes were isolated. Leukocytes were evaluated for membrane-associated Dectin-1 expression and cell phenotype by flow cytometry. MAIN RESULTS: In C. albicans infection, Dectin-1-positive blood and splenic leukocytes were increased from 23.5% to 58.9% over the course of infection. The increased percentage of Dectin-1-expressing cells was primarily attributable to neutrophilia. However, the amount of Dectin-1 expressed by blood and splenic neutrophils in C. albicans-infected mice was decreased by a range of 49.0% to 53.3%. C. albicans infection also resulted in an infiltration of Dectin-1-positive macrophages and neutrophils into the kidney. In contrast, polymicrobial sepsis decreased blood leukocyte Dectin-1-expressing cells by up to 51.4%. This reduction was due to a decrease in Dectin-1-positive neutrophils in the periphery. However, the percentage of Dectin-1-expressing cells in the peritoneal cavity increased by 774% with cecal ligation and puncture. Treatment of isolated neutrophils with three soluble glucans, mannan, lipopolysaccharide, or a variety of cytokines revealed that glucans, alone or in combination, were the only treatment that resulted in a decrease in Dectin-1-positive neutrophils. CONCLUSIONS: We conclude that peripheral leukocyte Dectin-1 expression is differentially regulated in fungal vs. polymicrobial sepsis. These data demonstrate that leukocyte Dectin-1 levels are modulated in response to infections of fungal and nonfungal origin.
Original languageEnglish
Pages (from-to)1038-1045
Number of pages8
JournalCritical Care Medicine
Volume37
Issue number3
DOIs
Publication statusPublished - Mar 2009

Keywords

  • animals
  • bacteremia
  • fungemia
  • leukocytes
  • membrane proteins
  • mice
  • mice, inbred ICR
  • nerve tissue proteins
  • dectin-1
  • glucan
  • Candida albicans
  • polymicrobial sepsis

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