Expression profile and function of triggering receptor expressed on myeloid cells-1 during melioidosis

Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies Toll-like receptor-initiated responses against pathogens. We aimed to characterize TREM-1 expression and function during sepsis caused by Burkholderia pseudomallei (melioidosis). TREM-1 expression was determined on leukocytes and pl...

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Vydané v:The Journal of infectious diseases Ročník 196; číslo 11; s. 1707
Hlavní autori: Wiersinga, W Joost, Veer, Cees van T, Wieland, Catharina W, Gibot, Sebastien, Hooibrink, Berend, Day, Nicholas P, Peacock, Sharon J, van der Poll, Tom
Médium: Journal Article
Jazyk:English
Vydavateľské údaje: United States 01.12.2007
Predmet:
Animals
Burkholderia pseudomallei
Case-Control Studies
Flow Cytometry
Gene Expression
Granulocytes - metabolism
Humans
Melioidosis - metabolism
Membrane Glycoproteins - biosynthesis
Membrane Glycoproteins - genetics
Mice
Monocytes - metabolism
Myeloid Cells - metabolism
Receptors, Immunologic - biosynthesis
Receptors, Immunologic - genetics
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - metabolism
Triggering Receptor Expressed on Myeloid Cells-1
ISSN:0022-1899
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Shrnutí:Triggering receptor expressed on myeloid cells-1 (TREM-1) amplifies Toll-like receptor-initiated responses against pathogens. We aimed to characterize TREM-1 expression and function during sepsis caused by Burkholderia pseudomallei (melioidosis). TREM-1 expression was determined on leukocytes and plasma from 34 patients with melioidosis and 32 controls and in mice with experimentally induced melioidosis. Responsiveness toward B. pseudomallei of TREM-1(+) and TREM-1(-) leukocytes was tested in vitro. TREM-1 function was inhibited in mice by a synthetic peptide mimicking the ectodomain of this receptor. Patients demonstrated increased soluble (s) TREM-1 plasma levels and TREM-1 surface expression on monocytes but not granulocytes. Similarly, mice inoculated with B. pseudomallei displayed a gradual rise in sTREM-1 level and an increase in blood monocyte but not granulocyte TREM-1 expression. At the primary infection site, however, granulocyte TREM-1 expression was enhanced, and the rise in sTREM-1 level occurred earlier. Additionally, purified human TREM-1(-) granulocytes showed reduced responsiveness to B. pseudomallei relative to TREM-1(+)granulocytes, a difference not detected for TREM-1(-) and TREM-1(+) monocytes. Treatment with a peptide mimicking a conserved domain of sTREM-1 partially protected mice from B. pseudomallei-induced lethality. During melioidosis, TREM-1 expression is differentially regulated on granulocytes and monocytes; measurement of TREM-1 expression on blood granulocytes may not provide adequate information on granulocyte TREM-1 expression at the infection site. TREM-1 may be a therapeutic target in melioidosis.
Bibliografia:ObjectType-Article-1
SourceType-Scholarly Journals-1
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content type line 23
ISSN:0022-1899
DOI:10.1086/522141