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

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 inf...

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Main Authors: Ozment-Skelton, T, deFluiter, E, Ha, T, Li, C, Graves, B, Ferguson, D, Schweitzer, J, Preizsner, J, Brown, G, Gordon, S, Kalbfleisch, J, Williams, D
Format: Journal article
Language:English
Published: 2009
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author Ozment-Skelton, T
deFluiter, E
Ha, T
Li, C
Graves, B
Ferguson, D
Schweitzer, J
Preizsner, J
Brown, G
Gordon, S
Kalbfleisch, J
Williams, D
author_facet Ozment-Skelton, T
deFluiter, E
Ha, T
Li, C
Graves, B
Ferguson, D
Schweitzer, J
Preizsner, J
Brown, G
Gordon, S
Kalbfleisch, J
Williams, D
author_sort Ozment-Skelton, T
collection OXFORD
description 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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spelling oxford-uuid:ded739f0-7433-4a4f-b4f5-2e95e62e9dc92022-03-27T09:35:07ZLeukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ded739f0-7433-4a4f-b4f5-2e95e62e9dc9EnglishSymplectic Elements at Oxford2009Ozment-Skelton, TdeFluiter, EHa, TLi, CGraves, BFerguson, DSchweitzer, JPreizsner, JBrown, GGordon, SKalbfleisch, JWilliams, DOBJECTIVE: 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.
spellingShingle Ozment-Skelton, T
deFluiter, E
Ha, T
Li, C
Graves, B
Ferguson, D
Schweitzer, J
Preizsner, J
Brown, G
Gordon, S
Kalbfleisch, J
Williams, D
Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title_full Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title_fullStr Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title_full_unstemmed Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title_short Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
title_sort leukocyte dectin 1 expression is differentially regulated in fungal versus polymicrobial sepsis
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