title: Low invasiveness of pneumococcal serotype 11A is linked to ficolin-2 recognition of O-acetylated capsule epitopes and lectin complement pathway activation.
abstract: BACKGROUND
  The divergent epidemiological behavior of Streptococcus pneumoniae serotypes suggests that serotype-specific features such as capsule O-acetylation influence the propensity of a strain to cause invasive pneumococcal disease (IPD). We hypothesize that innate host factors mediate the observed negative association between IPD and the serotype 11A (ST11A) capsule O-acetyltransferase gene, wcjE.
  
  
  METHODS
  We evaluated the ability of ficolin-2, an initiator of the lectin complement pathway that was previously shown to bind ST11A pneumococci, to recognize and mediate complement-dependent opsonophagocytosis of different pneumococcal serotypes. We supplemented findings with an epidemiological meta-analysis comparing invasiveness of the 30 most prevalent pneumococcal serotypes.
  
  
  RESULTS
  Ficolin-2 bound ST11A capsule polysaccharide and other wcjE-containing pneumococcal serotypes, except ST9V and ST20B. Ficolin-2 did not bind wcjE-null serotypes, including the wcjE-null variant of ST11A, ST11E. We observed C1q-independent complement deposition and phagocytic killing of pneumococci expressing ST11A but not those expressing ST11E. Inhibition of ficolin-2 binding abrogated ST11A-associated complement deposition and phagocytosis. In children, invasiveness of ST11A was the lowest among serotypes tested in our meta-analysis, while ST9V was among the highest.
  
  
  CONCLUSIONS
  Ficolin-2 mediates serum protection by recognizing specific O-acetylated epitopes of pneumococcal capsule polysaccharides, exemplifying a novel host-microbe interaction that innately offers serotype-specific immunity to IPD.
authors.affiliation: Department of Pathology.
authors.forename: Allison M
authors.initials: AM
authors.lastname: Brady
authors.affiliation: Department of Pathology.
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Calix
authors.affiliation: Department of Pathology.
authors.forename: Jigui
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Pathology.
authors.forename: Kimball Aaron
authors.initials: KA
authors.lastname: Geno
authors.affiliation: School of Public Health, University of Alabama at Birmingham.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: Department of Pathology Department of Microbiology.
authors.forename: Moon H
authors.initials: MH
authors.lastname: Nahm
mesh_terms: D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002648:Child; D002675:Child, Preschool; D037582:Complement Pathway, Mannose-Binding Lectin / Q000276:immunology*; D000939:Epitopes / Q000276:immunology*; D054884:Host-Pathogen Interactions; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D037102:Lectins / Q000276:immunology / Q000378:metabolism*; D009895:Opsonin Proteins / Q000276:immunology; D010587:Phagocytosis; D011485:Protein Binding; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology*; D000097604:Ficolins
chemical_list: D000907:Antibodies, Bacterial; D000939:Epitopes; D037102:Lectins; D009895:Opsonin Proteins; D000097604:Ficolins
keywords: Streptococcus pneumoniae; complement; ficolin-2; invasiveness; serotype 11A