• W Joost Wiersinga, Cees van T Veer, Catharina W Wieland, Sebastien Gibot, Berend Hooibrink, Nicholas P Day, Sharon J Peacock, and Tom van der Poll.
• Center for Infection and Immunity Amsterdam, Amsterdam, 1105 AZ, The Netherlands. w.j.wiersinga@amc.uva.nl
• J. Infect. Dis. 2007 Dec 1;196(11):1707-16.

BackgroundTriggering 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).MethodsTREM-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.ResultsPatients 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.ConclusionsDuring 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.

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