title: The lectin-like domain of thrombomodulin hampers host defence in pneumococcal pneumonia.
abstract: The lectin-like domain of thrombomodulin (TM) plays an important regulatory role in sterile inflammatory conditions, but its role in severe Gram-positive infectious disease is unknown. Streptococcus pneumoniae is the most common cause of community-acquired pneumonia. The aim of this study was to determine the role of the lectin-like domain of TM in murine pneumococcal pneumonia. Wild-type (WT) mice and mice lacking the lectin-like domain of TM (TM(LeD/LeD)) were infected intranasally with viable S. pneumoniae and either observed in a survival study or euthanised 6, 24 or 48 h after infection. TM(LeD/LeD) mice had a markedly better survival in pneumococcal pneumonia when compared with WT mice. At 48 h post-infection with S. pneumoniae, TM(LeD/LeD) mice had lower bacterial loads in blood and liver, and exhibited less pulmonary inflammation, as shown by having less lung histopathology, less neutrophil influx and lower cytokine and chemokine levels. Plasma levels of pro-inflammatory cytokines were also reduced in TM(LeD/LeD) mice after exposure to the infection. Deletion of the lectin-like domain of TM improves the host defence in pneumococcal pneumonia. The lectin-like domain of TM may have a differential role in response to Gram-positive or Gram-negative bacteria.
authors.affiliation: Center for Experimental and Molecular Medicine,Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Schouten
authors.forename: J Daan
authors.initials: JD
authors.lastname: de Boer
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.forename: Joris J T H
authors.initials: JJ
authors.lastname: Roelofs
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Edward M
authors.initials: EM
authors.lastname: Conway
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D058491:Bacterial Load; D001777:Blood Coagulation; D018893:Bronchoalveolar Lavage; D016207:Cytokines / Q000097:blood / Q000276:immunology; D004195:Disease Models, Animal; D007249:Inflammation / Q000276:immunology; D037102:Lectins / Q000737:chemistry*; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D054730:Protein Interaction Domains and Motifs; D018805:Sepsis / Q000378:metabolism; D018180:Thrombomodulin / Q000737:chemistry*
chemical_list: D016207:Cytokines; D037102:Lectins; D018180:Thrombomodulin