title: Role of triggering receptor expressed on myeloid cells-1/3 in Klebsiella-derived pneumosepsis.
abstract: Triggering receptor expressed on myeloid cells (TREM)-1 and -2 can affect Toll-like receptor-mediated activation of immune cells. Klebsiella pneumoniae is a common cause of pneumonia-derived sepsis. Here we studied the role of TREM-1/3 and TREM-2 in the host response during Klebsiella pneumonia. Macrophages lacking either TREM-1/3 or TREM-2 were tested for their responsiveness toward K. pneumoniae and for their capacity to internalize this pathogen in vitro. TREM-1/3- and TREM-2-deficient mice were infected with K. pneumoniae via the airways, and their responses were compared with those in wild-type mice. TREM-1/3-deficient macrophages produced lower cytokine levels upon exposure to K. pneumoniae, whereas TREM-2-deficient macrophages released higher cytokine concentrations. TREM-2-deficient, but not TREM-1/3-deficient, macrophages showed a reduced capacity to phagocytose K. pneumoniae. TREM-1/3-deficient mice showed an impaired host defense during Klebsiella pneumonia, as reflected by worsened survival and increased bacterial growth and dissemination. In contrast, TREM-2 deficiency did not affect disease outcome. Although TREM-1/3 and TREM-2 influence macrophage responsiveness to K. pneumoniae in vitro, only TREM-1/3 contribute to the host response during Klebsiella pneumonia in vivo, serving a protective role.
authors: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors: Tijmen J
authors: TJ
authors: Hommes
authors: 3 Department of Pathology, and.
authors: Mark C
authors: MC
authors: Dessing
authors: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors: Cornelis van 't
authors: Cv
authors: Veer
authors: 3 Department of Pathology, and.
authors: Sandrine
authors: S
authors: Florquin
authors: 4 Department of Pathology, Washington University in St. Louis, St. Louis, Missouri.
authors: Marco
authors: M
authors: Colonna
authors: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.
authors: Alex F
authors: AF
authors: de Vos
authors: 1 Center for Experimental and Molecular Medicine.|2 Center for Infection and Immunity.|5 Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands; and.
authors: Tom
authors: T
authors: van der Poll
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D007711:Klebsiella pneumoniae / Q000254:growth & development / Q000276:immunology; D008168:Lung / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010587:Phagocytosis; D018410:Pneumonia, Bacterial / Q000235:genetics / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D061251:Primary Cell Culture; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D018805:Sepsis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D015398:Signal Transduction; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: D018925:Chemokines; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; C498716:Trem2 protein, mouse; C447602:Trem3 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; C074302:keratinocyte-derived chemokines
keywords: Klebsiella pneumoniae; TREM-1; TREM-2; macrophages; pneumonia