title: Leukocyte Dectin-1 expression is differentially regulated in fungal versus polymicrobial sepsis.
abstract: OBJECTIVE
  To examine peripheral leukocyte Dectin-1 regulation in clinically relevant models of fungal and polymicrobial sepsis.
  
  
  METHODS
  Prospective animal study.
  
  
  METHODS
  University medical school research laboratory.
  
  
  METHODS
  Age, weight, and sex matched ICR/HSD mice.
  
  
  METHODS
  Mice were infected with Candida albicans (1 x 10, intravenously) or were subjected to cecal ligation and puncture to induce polymicrobial sepsis.
  
  
  METHODS
  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.
  
  
  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.
authors.affiliation: Departments of Surgery, Microbiology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
authors.forename: Tammy R
authors.initials: TR
authors.lastname: Ozment-Skelton
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: deFluiter
authors.forename: Tuanzhu
authors.initials: T
authors.lastname: Ha
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Bridget M
authors.initials: BM
authors.lastname: Graves
authors.forename: Donald A
authors.initials: DA
authors.lastname: Ferguson
authors.forename: John B
authors.initials: JB
authors.lastname: Schweitzer
authors.forename: Johanna
authors.initials: J
authors.lastname: Preizsner
authors.forename: Gordon D
authors.initials: GD
authors.lastname: Brown
authors.forename: Siamon
authors.initials: S
authors.lastname: Gordon
authors.forename: John H
authors.initials: JH
authors.lastname: Kalbfleisch
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000276:immunology*; D016469:Fungemia / Q000276:immunology*; D037181:Lectins, C-Type; D007962:Leukocytes / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008813:Mice, Inbred ICR; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D000099181:Dectin-1
chemical_list: D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1