Low invasiveness of pneumococcal serotype 11A is linked to ficolin-2 recognition of O-acetylated capsule epitopes and lectin complement pathway activation

J Infect Dis. 2014 Oct 1;210(7):1155-65. doi: 10.1093/infdis/jiu195. Epub 2014 Mar 27.


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.

Keywords: Streptococcus pneumoniae; complement; ficolin-2; invasiveness; serotype 11A.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Bacterial / immunology
  • Bacterial Capsules / immunology*
  • Blood Bactericidal Activity
  • Child
  • Child, Preschool
  • Complement Pathway, Mannose-Binding Lectin / immunology*
  • Epitopes / immunology*
  • Ficolins
  • Host-Pathogen Interactions
  • Humans
  • Infant
  • Infant, Newborn
  • Lectins / immunology
  • Lectins / metabolism*
  • Opsonin Proteins / immunology
  • Phagocytosis
  • Protein Binding
  • Serogroup
  • Streptococcus pneumoniae / classification
  • Streptococcus pneumoniae / immunology*


  • Antibodies, Bacterial
  • Epitopes
  • Lectins
  • Opsonin Proteins