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Type: Journal article
Title: Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia
Author: Yuste, J.
Botto, M.
Paton, J.
Holden, D.
Brown, J.
Citation: Journal of Immunology, 2005; 175(3):1813-1819
Publisher: Amer Assoc Immunologists
Issue Date: 2005
ISSN: 0022-1767
Statement of
Jose Yuste, Marina Botto, James C. Paton, David W. Holden and Jeremy S. Brown
Abstract: Streptococcus pneumoniae is a common cause of septicemia in the immunocompetent host. To establish infection, S. pneumoniae has to overcome host innate immune responses, one component of which is the complement system. Using isogenic bacterial mutant strains and complement-deficient immune naive mice, we show that the S. pneumoniae virulence factor pneumolysin prevents complement deposition on S. pneumoniae, mainly through effects on the classical pathway. In addition, using a double pspA–/ply– mutant strain we demonstrate that pneumolysin and the S. pneumoniae surface protein PspA act in concert to affect both classical and alternative complement pathway activity. As a result, the virulence of the pspA–/ply– strain in models of both systemic and pulmonary infection is greatly attenuated in wild-type mice but not complement deficient mice. The sensitivity of the pspA–/ply– strain to complement was exploited to demonstrate that although early innate immunity to S. pneumoniae during pulmonary infection is partially complement-dependent, the main effect of complement is to prevent spread of S. pneumoniae from the lungs to the blood. These data suggest that inhibition of complement deposition on S. pneumoniae by pneumolysin and PspA is essential for S. pneumoniae to successfully cause septicemia. Targeting mechanisms of complement inhibition could be an effective therapeutic strategy for patients with septicemia due to S. pneumoniae or other bacterial pathogens.
Keywords: Animals
Mice, Inbred C57BL
Mice, Knockout
Streptococcus pneumoniae
Pneumococcal Infections
Complement Factor B
Bacterial Proteins
Heat-Shock Proteins
Virulence Factors
Complement Pathway, Classical
Drug Synergism
Complement System Proteins
Complement Inactivator Proteins
Complement C3
Complement C1q
Rights: © 2005 by The American Association of Immunologists
DOI: 10.4049/jimmunol.175.3.1813
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Appears in Collections:Aurora harvest 6
Molecular and Biomedical Science publications

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