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

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 t... Full description

Journal Title: Proceedings of the National Academy of Sciences of the United States of America 24 December 2002, Vol.99(26), p.16969
Main Author: Jeremy S. Brown
Other Authors: Tracy Hussell , Sarah M. Gilliland , David W. Holden , James C. Paton , Michael R. Ehrenstein , Mark J. Walport , Marina Botto
Format: Electronic Article Electronic Article
Language: English
Subjects:
ID: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.012669199
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recordid: pnas_s99_26_16969
title: The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice
format: Article
creator:
  • Jeremy S. Brown
  • Tracy Hussell
  • Sarah M. Gilliland
  • David W. Holden
  • James C. Paton
  • Michael R. Ehrenstein
  • Mark J. Walport
  • Marina Botto
subjects:
  • Sciences (General)
ispartof: Proceedings of the National Academy of Sciences of the United States of America, 24 December 2002, Vol.99(26), p.16969
description: 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.
language: eng
source:
identifier: ISSN: 0027-8424 ; E-ISSN: 1091-6490 ; DOI: 10.1073/pnas.012669199
fulltext: fulltext_linktorsrc
issn:
  • 0027-8424
  • 00278424
  • 1091-6490
  • 10916490
url: Link


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titleThe classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice
creatorJeremy S. Brown ; Tracy Hussell ; Sarah M. Gilliland ; David W. Holden ; James C. Paton ; Michael R. Ehrenstein ; Mark J. Walport ; Marina Botto
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descriptionThe 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.
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titleThe classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice
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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.

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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.

pubNational Acad Sciences
doi10.1073/pnas.012669199
urlhttp://www.pnas.org/content/99/26/16969.abstract
lad01Proceedings of the National Academy of Sciences of the United States of America
pages16969-16974
date2002-12-24