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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Wiersinga
W Joost
WJ
Center for Infection and Immunity Amsterdam, Amsterdam, 1105 AZ, The Netherlands. w.j.wiersinga@amc.uva.nl
Veer
Cees van T
Cv
Wieland
Catharina W
CW
Gibot
Sebastien
S
Hooibrink
Berend
B
Day
Nicholas P
NP
Peacock
Sharon J
SJ
van der Poll
Tom
T
D000818:Animals; D016957:Burkholderia pseudomallei; D016022:Case-Control Studies; D005434:Flow Cytometry; D015870:Gene Expression; D006098:Granulocytes / Q000378:metabolism*; D006801:Humans; D008554:Melioidosis / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D009000:Monocytes / Q000378:metabolism*; D022423:Myeloid Cells / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011971:Receptors, Immunologic; C408842:TREM1 protein, human; D000073871:Triggering Receptor Expressed on Myeloid Cells-1