title: Role of Nucleotide-Binding Oligomerization Domain-Containing (NOD) 2 in Host Defense during Pneumococcal Pneumonia.
abstract: Streptococcus (S.) pneumoniae is the most common causative pathogen in community-acquired pneumonia. Nucleotide-binding oligomerization domain-containing (NOD) 2 is a pattern recognition receptor located in the cytosol of myeloid cells that is able to detect peptidoglycan fragments of S. pneumoniae. We here aimed to investigate the role of NOD2 in the host response during pneumococcal pneumonia. Phagocytosis of S. pneumoniae was studied in NOD2 deficient (Nod2-/-) and wild-type (Wt) alveolar macrophages and neutrophils in vitro. In subsequent in vivo experiments Nod2-/- and Wt mice were inoculated with serotype 2 S. pneumoniae (D39), an isogenic capsule locus deletion mutant (D39Δcps) or serotype 3 S. pneumoniae (6303) via the airways, and bacterial growth and dissemination and the lung inflammatory response were evaluated. Nod2-/- alveolar macrophages and blood neutrophils displayed a reduced capacity to internalize pneumococci in vitro. During pneumonia caused by S. pneumoniae D39 Nod2-/- mice were indistinguishable from Wt mice with regard to bacterial loads in lungs and distant organs, lung pathology and neutrophil recruitment. While Nod2-/- and Wt mice also had similar bacterial loads after infection with the more virulent S. pneumoniae 6303 strain, Nod2-/- mice displayed a reduced bacterial clearance of the normally avirulent unencapsulated D39Δcps strain. These results suggest that NOD2 does not contribute to host defense during pneumococcal pneumonia and that the pneumococcal capsule impairs recognition of S. pneumoniae by NOD2.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tijmen J
authors.initials: TJ
authors.lastname: Hommes
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Miriam H
authors.initials: MH
authors.lastname: van Lieshout
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Sandrine
authors.initials: S
authors.lastname: Florquin
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Hester J
authors.initials: HJ
authors.lastname: Bootsma
authors.affiliation: Laboratory of Pediatric Infectious Diseases, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Hermans
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Center for Infection and Immunity, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.|Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics; D016676:Macrophages, Alveolar / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000276:immunology / Q000382:microbiology; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D010587:Phagocytosis; D011018:Pneumonia, Pneumococcal / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000235:genetics / Q000472:pathogenicity
chemical_list: D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse