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Chapter 7 : Interactions of Streptococcus pneumoniae with Complement Proteins
Category: Bacterial Pathogenesis; Immunology
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This chapter briefly reviews some salient features of complement-mediated opsonophagocytosis. It discusses the inhibitory mechanisms attributed to specific pneumococcal proteins and polysaccharides, and reviews the human immunodeficiencies of particular relevance to complement-mediated killing of Streptococcus pneumoniae. Traditionally, the binding of complement protein C1q to the Fc portion of either pentavalent immunoglobulin M (IgM) or IgG initiates the classical complement pathway. The mannose-binding lectin (MBL) complex, composed of three to six subunits of MBL, preferentially recognizes mannose, mannans, and N-acetylglucosamine (GlcNAc). The integrity of the alternative complement pathway is thought to be critical for those hosts lacking type-specific anticapsular antibodies or proteins required for classical pathway activation (e.g., C2). Comparative studies of pneumococcal bacteremia in C57BL/6 mice genetically deficient in C1q, factor B (encoded by Bf), C3, C4, or natural IgM pointed to the importance of the classical complement pathway in the absence of IgG. Exponentially growing wild-type S. pneumoniae strains of serotypes 3, 4, and 14 are able to degrade both α- and β-chains of purified human C3 in the absence of other serum proteins. The release of pneumolysin (Ply) during autolysis leads to the activation of the classical complement pathway, possibly through the binding of the Fc portion of IgG. At least six pneumococcal proteins—pneumolysin, PhpA, Hic, PspC (CbpA/SpsA/PbcA), PspA, and CppA—are now known to interfere with complement-mediated opsonization and phagocytic killing.
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Diagram of the three pathways of complement activation. Each convertase cleaves circulating C3 and results in the deposition of C3b onto the pathogen. Interaction with factors H and I cleaves C3b to iC3b, C3c, and C3d. Serving as ligands for complement receptors on leukocytes, iC3b and C3d mediate phagocytic killing and antibody response, respectively. Adapted from Cell ( 64 ) with permission of the publisher.
Role of CRs in pneumococcal pathogenesis
Mechanisms of pneumococcal interference with complement pathways