W. Joost WiersingaCees Van 'T VeerCatharina W. WielandSebastien GibotBerend HooibrinkNicholas P. DaySharon J. PeacockTom Van Der PollCenter for Infection and Immunity Amsterdam (CINIMA)Academic Medical Centre, University of AmsterdamCHU de NancyMahidol UniversityNuffield Department of Clinical Medicine2018-08-242018-08-242007-12-01Journal of Infectious Diseases. Vol.196, No.11 (2007), 1707-1716002218992-s2.0-38449106594https://repository.li.mahidol.ac.th/handle/20.500.14594/24665Background. 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. © 2007 by the Infectious Diseases Society of America. All rights reserved.Mahidol UniversityMedicineArticleSCOPUS10.1086/522141