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

8 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

Fingerprint

Sepsis
Leukocytes
Neutrophils
Candida albicans
Glucans
Punctures
Ligation
dectin 1
Infection
Mannans
Inbred ICR Mouse
Mycoses
Peritoneal Cavity
Exudates and Transudates
Medical Schools
Lipopolysaccharides
Biomedical Research
Flow Cytometry
Spleen
Macrophages

Keywords

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

Cite this

Ozment-Skelton, T. R., deFluiter, E. A., Ha, T., Li, C., Graves, B. M., Ferguson, D. A., ... Williams, D. L. (2009). Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis. Critical Care Medicine, 37(3), 1038-1045. https://doi.org/10.1097/CCM.0b013e3181968fa0

Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis. / Ozment-Skelton, Tammy R; deFluiter, Elizabeth A; Ha, Tuanzhu; Li, Chan; Graves, Bridget M; Ferguson, Donald A.; Schweitzer, John B; Preizsner, Johanna; Brown, Gordon D; Gordon, Siamon; Kalbfleisch, John H; Williams, David L.

In: Critical Care Medicine, Vol. 37, No. 3, 03.2009, p. 1038-1045.

Research output: Contribution to journalArticle

Ozment-Skelton, TR, deFluiter, EA, Ha, T, Li, C, Graves, BM, Ferguson, DA, Schweitzer, JB, Preizsner, J, Brown, GD, Gordon, S, Kalbfleisch, JH & Williams, DL 2009, 'Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis', Critical Care Medicine, vol. 37, no. 3, pp. 1038-1045. https://doi.org/10.1097/CCM.0b013e3181968fa0
Ozment-Skelton, Tammy R ; deFluiter, Elizabeth A ; Ha, Tuanzhu ; Li, Chan ; Graves, Bridget M ; Ferguson, Donald A. ; Schweitzer, John B ; Preizsner, Johanna ; Brown, Gordon D ; Gordon, Siamon ; Kalbfleisch, John H ; Williams, David L. / Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis. In: Critical Care Medicine. 2009 ; Vol. 37, No. 3. pp. 1038-1045.
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AU - Ozment-Skelton, Tammy R

AU - deFluiter, Elizabeth A

AU - Ha, Tuanzhu

AU - Li, Chan

AU - Graves, Bridget M

AU - Ferguson, Donald A.

AU - Schweitzer, John B

AU - Preizsner, Johanna

AU - Brown, Gordon D

AU - Gordon, Siamon

AU - Kalbfleisch, John H

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N2 - 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.

AB - 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.

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KW - nerve tissue proteins

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KW - glucan

KW - Candida albicans

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