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Additive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia

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dc.contributor.authorYuste, J.
dc.contributor.authorBotto, M.
dc.contributor.authorPaton, J.
dc.contributor.authorHolden, D.
dc.contributor.authorBrown, J.
dc.date.issued2005
dc.description.abstractStreptococcus 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.
dc.description.statementofresponsibilityJose Yuste, Marina Botto, James C. Paton, David W. Holden and Jeremy S. Brown
dc.identifier.citationJournal of Immunology, 2005; 175(3):1813-1819
dc.identifier.doi10.4049/jimmunol.175.3.1813
dc.identifier.issn0022-1767
dc.identifier.issn1550-6606
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.urihttp://hdl.handle.net/2440/27575
dc.language.isoen
dc.publisherAmer Assoc Immunologists
dc.rights© 2005 by The American Association of Immunologists
dc.source.urihttp://www.jimmunol.org/cgi/content/abstract/175/3/1813
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectStreptococcus pneumoniae
dc.subjectPneumococcal Infections
dc.subjectSepsis
dc.subjectComplement Factor B
dc.subjectBacterial Proteins
dc.subjectHeat-Shock Proteins
dc.subjectStreptolysins
dc.subjectVirulence Factors
dc.subjectComplement Pathway, Classical
dc.subjectDrug Synergism
dc.subjectComplement System Proteins
dc.subjectComplement Inactivator Proteins
dc.subjectComplement C3
dc.subjectComplement C1q
dc.titleAdditive inhibition of complement deposition by pneumolysin and PspA facilitates Streptococcus pneumoniae septicemia
dc.typeJournal article
pubs.publication-statusPublished

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