title: Triggering receptor expressed on myeloid cells-1 (TREM-1) improves host defence in pneumococcal pneumonia.
abstract: Streptococcus (S.) pneumoniae is a common Gram-positive pathogen in community-acquired pneumonia and sepsis. Triggering receptor expressed on myeloid cells-1 (TREM-1) is a receptor on phagocytes known to amplify inflammatory responses. Previous studies showed that TREM-1 inhibition protects against lethality during experimental Gram-negative sepsis. We here aimed to investigate the role of TREM-1 in an experimental model of pneumococcal pneumonia, using TREM-1/3-deficient (Trem-1/3(-/-) ) and wild-type (Wt) mice. Additionally ex vivo responsiveness of Trem-1/3(-/-) neutrophils and macrophages was examined. S. pneumoniae infection resulted in a rapid recruitment of TREM-1-positive neutrophils into the bronchoalveolar space, while high constitutive TREM-1 expression on alveolar macrophages remained unchanged. TREM-1/3 deficiency led to increased lethality, accompanied by enhanced growth of S. pneumoniae at the primary site of infection and increased dissemination to distant organs. Within the first 3-6 h of infection, Trem-1/3(-/-) mice demonstrated a strongly impaired innate immune response in the airways, as reflected by reduced local release of cytokines and chemokines and a delayed influx of neutrophils. Trem-1/3(-/-) alveolar macrophages produced fewer cytokines upon exposure to S. pneumoniae in vitro and were less capable of phagocytosing this pathogen. TREM-1/3 deficiency did not influence neutrophil responsiveness to S. pneumoniae. These results identify TREM-1 as a key player in protective innate immunity during pneumococcal pneumonia, most likely by enhancing the early immune response of alveolar macrophages.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Centre, University of Amsterdam, The Netherlands; Centre for Infection and Immunity, Academic Medical Centre, University of Amsterdam, The Netherlands.
authors.forename: Tijmen J
authors.initials: TJ
authors.lastname: Hommes
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
authors.forename: Cornelis
authors.initials: C
authors.lastname: Van't Veer
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.forename: Marco
authors.initials: M
authors.lastname: Colonna
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D002465:Cell Movement; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007113:Immunity, Innate / Q000502:physiology*; D016676:Macrophages, Alveolar / Q000378:metabolism / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000378:metabolism / Q000473:pathology; D011018:Pneumonia, Pneumococcal / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D011971:Receptors, Immunologic / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013296:Streptococcus pneumoniae; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
chemical_list: D016207:Cytokines; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; C517262:TREM1 protein, mouse; D000073871:Triggering Receptor Expressed on Myeloid Cells-1
keywords: TREM-1; innate immunity; macrophages; phagocytosis; pneumococcal pneumonia