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.


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.
Ozment-Skelton
Tammy R
TR
Departments of Surgery, Microbiology, Quillen College of Medicine, East Tennessee State University, Johnson City, TN, USA.
deFluiter
Elizabeth A
EA
Ha
Tuanzhu
T
Li
Chuanfu
C
Graves
Bridget M
BM
Ferguson
Donald A
DA
Schweitzer
John B
JB
Preizsner
Johanna
J
Brown
Gordon D
GD
Gordon
Siamon
S
Kalbfleisch
John H
JH
Williams
David L
DL
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
D037181:Lectins, C-Type; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000099181:Dectin-1