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.
|Number of pages||10|
|Journal||Journal of Infectious Diseases|
|Publication status||Published - 1 Dec 2007|
Bibliographical noteFunding Information:
Received 15 December 2006; accepted 17 May 2007; electronically published 25 October 2007. Potential conflicts of interest: none reported. Financial support: Dutch Foundation for Tropical Research (WOTRO), The Netherlands (support to W.J.W.); Wellcome Trust, United Kingdom (S.J.P. is a Wellcome Trust Career Development Fellow). Presented in part: Interscience Conference on Antimicrobial Agents and Chemotherapy, American Society for Microbiology, San Francisco, 17–20 September 2006. Reprints or correspondence: Dr. W. J. Wiersinga, Academic Medical Center, Center for Experimental and Molecular Medicine, Meibergdreef 9, Rm. G2-132, 1105 AZ Amsterdam, The Netherlands (email@example.com).