title: The polysaccharide capsule of Streptococcus pneumonia partially impedes MyD88-mediated immunity during pneumonia in mice.
abstract: Toll-like receptors (TLR) and the downstream adaptor protein MyD88 are considered crucial for protective immunity during bacterial infections. Streptococcus (S.) pneumoniae is a human respiratory pathogen and a large majority of clinical pneumococcal isolates expresses an external polysaccharide capsule. We here sought to determine the role of pneumococcal capsule in MyD88-mediated antibacterial defense during S. pneumonia pneumonia. Wild type (WT) and Myd88(-/-) mice were inoculated intranasally with serotype 2 S. pneumoniae D39 or with an isogenic capsule locus deletion mutant (D39∆cps), and analysed for bacterial outgrowth and inflammatory responses in the lung. As compared to WT mice, Myd88(-/-) mice infected with D39 demonstrated a modestly impaired bacterial clearance accompanied by decreased inflammatory responses in the lung. Strikingly, while WT mice rapidly cleared D39∆cps, Myd88(-/-) mice showed 105-fold higher bacterial burdens in their lungs and dissemination to blood 24 hours after infection. These data suggest that the pneumococcal capsule impairs recognition of TLR ligands expressed by S. pneumoniae and thereby partially impedes MyD88-mediated antibacterial defense.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), 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 of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Mark C
authors.initials: MC
authors.lastname: Dessing
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Adriana J J
authors.initials: AJ
authors.lastname: Lammers
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Alexander P N A
authors.initials: AP
authors.lastname: de Porto
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: Department of Pathology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Onno J
authors.initials: OJ
authors.lastname: de Boer
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Regina
authors.initials: R
authors.lastname: de Beer
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Sanne
authors.initials: S
authors.lastname: Terpstra
authors.affiliation: Radboud University Medical Center, Laboratory of Pediatric Infectious Diseases, Nijmegen, The Netherlands.
authors.forename: Hester J
authors.initials: HJ
authors.lastname: Bootsma
authors.affiliation: Radboud University Medical Center, Laboratory of Pediatric Infectious Diseases, 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 of Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Cornelis
authors.initials: C
authors.lastname: van 't Veer
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands; Center of Infection and Immunity Amsterdam (CINIMA), 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 / Q000276:immunology*; D017353:Gene Deletion; D051379:Mice; D008810:Mice, Inbred C57BL; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics* / Q000276:immunology; D018410:Pneumonia, Bacterial / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial