Species-Specific Interaction of Streptococcus pneumoniae with Human Complement Factor H

Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
The Journal of Immunology (Impact Factor: 4.92). 12/2008; 181(10):7138-46. DOI: 10.4049/jimmunol.181.10.7138
Source: PubMed


Streptococcus pneumoniae naturally colonizes the nasopharynx as a commensal organism and sometimes causes infections in remote tissue sites. This bacterium is highly capable of resisting host innate immunity during nasopharyngeal colonization and disseminating infections. The ability to recruit complement factor H (FH) by S. pneumoniae has been implicated as a bacterial immune evasion mechanism against complement-mediated bacterial clearance because FH is a complement alternative pathway inhibitor. S. pneumoniae recruits FH through a previously defined FH binding domain of choline-binding protein A (CbpA), a major surface protein of S. pneumoniae. In this study, we show that CbpA binds to human FH, but not to the FH proteins of mouse and other animal species tested to date. Accordingly, deleting the FH binding domain of CbpA in strain D39 did not result in obvious change in the levels of pneumococcal bacteremia or virulence in a bacteremia mouse model. Furthermore, this species-specific pneumococcal interaction with FH was shown to occur in multiple pneumococcal isolates from the blood and cerebrospinal fluid. Finally, our phagocytosis experiments with human and mouse phagocytes and complement systems provide additional evidence to support our hypothesis that CbpA acts as a bacterial determinant for pneumococcal resistance to complement-mediated host defense in humans.

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Available from: Zhuo Ma, Mar 03, 2014
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    • "The reduced capacity of complement mediated opsonization and phagocytosis in complementdeficient mice appear to be responsible for the impaired clearance of Spn from the middle ear and dissemination to the blood stream during AOM [12] [13]. However, Spn can evade the complement system by several mechanisms, including recruitment of the host complement regulators C4b binding protein (C4BP) or factor H (FH) to the bacterial surface to inhibit the classical and alternative complement pathways respectively [14] [15]. Little is known about the ability of the complement system to enable killing of Spn opacity variants during the course of pneumococcal OM. "
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