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

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

Author information

1
Department of Pathology.
2
School of Public Health, University of Alabama at Birmingham.
3
Department of Pathology Department of Microbiology.

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.

KEYWORDS:

Streptococcus pneumoniae; complement; ficolin-2; invasiveness; serotype 11A

PMID:
24683196
PMCID:
PMC4215079
DOI:
10.1093/infdis/jiu195
[Indexed for MEDLINE]
Free PMC Article

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