The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice

Jeremy S. Brown, Tracy Hussell, Sarah M. Gilliland, David W. Holden, James C. Paton, Michael R. Ehrenstein, Mark J. Walport, Marina Botto

    Research output: Contribution to journalArticlepeer-review

    Abstract

    The complement system is an important component of the innate immune response to bacterial pathogens, including Streptococcus pneumoniae. The classical complement pathway is activated by antibody-antigen complexes on the bacterial surface and has been considered predominately to be an effector of the adaptive immune response, whereas the alternative and mannose-binding lectin pathways are activated directly by bacterial cell surface components and are considered effectors of the innate immune response. Recently, a role has been suggested for the classical pathway during innate immunity that is activated by natural IgM or components of the acute-phase response bound to bacterial pathogens. However, the functional importance of the classical pathway for innate immunity to S. pneumoniae and other bacterial pathogens, and its relative contribution compared with the alternative and mannose-binding lectin pathways has not been defined. By using strains of mice with genetic deficiencies of complement components and secretory IgM we have investigated the role of each complement pathway and natural IgM for innate immunity to S. pneumoniae. Our results show that the proportion of a population of S. pneumoniae bound by C3 depends mainly on the classical pathway, whereas the intensity of C3 binding depends on the alternative pathway. Furthermore, the classical pathway, partially targeted by the binding of natural IgM to bacteria, is the dominant pathway for activation of the complement system during innate immunity to S. pneumoniae, loss of which results in rapidly progressing septicemia and impaired macrophage activation. These data demonstrate the vital role of the classical pathway for innate immunity to a bacterial pathogen.
    Original languageEnglish
    Pages (from-to)16969-16974
    Number of pages5
    JournalProceedings of the National Academy of Sciences of the United States of America
    Volume99
    Issue number26
    DOIs
    Publication statusPublished - 24 Dec 2002

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