Clinical isolates of Streptococcus pneumoniae bind the complement inhibitor C4b-binding protein in a PspC allele-dependent fashion.

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Abstract

The complement system constitutes an important component of the innate immune system. To colonize their host and/or to cause disease, many pathogens have evolved strategies to avoid complement-mediated bacterial lysis and opsonophagocytosis. In this study, using a collection of 55 clinical isolates of Streptococcus pneumoniae, we demonstrate for the first time that pneumococci bind the complement inhibitor C4b-binding protein (C4BP). C4BP binding seems to be restricted to certain serotypes such as serotype 4, 6B, 7F, and 14, of which the strains of serotype 14 are the strongest binders. We show that bacteria-bound C4BP retains its functional activity and down-regulates the activation of the classical pathway. Thus, this major respiratory pathogen may escape immune recognition and eradication by the complement system. Furthermore, we show that C4BP binding varies between strains but is dependent on the expression of pneumococcal surface protein C, PspC of group 4. The study of the distribution of group 4 pspC locus shows that most of high-binder serotype 14 isolates harbor an allelic variant of group 4 pspC. Using PspC-negative mutant strains, we identified a new allelic variant of PspC (PspC4.4) as a major ligand for C4BP, revealing a new function for this important pneumococcal virulence factor. Thus pneumococci exploit host C4BP for complement evasion in a PspC allele-dependent manner.

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Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • Bacterial Proteins: metabolism, Bacterial Proteins: genetics, Bacterial Proteins: immunology, Complement C4b-Binding Protein: genetics, Complement C4b-Binding Protein: immunology, Complement C4b-Binding Protein: metabolism, Mutation: genetics, Streptococcus pneumoniae: genetics, Streptococcus pneumoniae: immunology, Streptococcus pneumoniae: metabolism, Streptococcus pneumoniae: isolation & purification
Original languageEnglish
Pages (from-to)7865-7877
JournalJournal of Immunology
Volume182
Issue number12
Publication statusPublished - 2009
Publication categoryResearch
Peer-reviewedYes