ArticleProceedings of the National Academy of Sciences of the United States of America2002
The classical pathway is the dominant complement pathway required for innate immunity to Streptococcus pneumoniae infection in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 177 papers, 1 of them a synthesis that pooled it.
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177 citing papers in PubMed, 1 synthesis or guideline pooled it.
- C1q as a target molecule to treat human disease: What do mouse studies teach us?Frontiers in immunology · 2022Pooled it
- Trial
- 3' UTR-mediated regulation of a protein chaperone by the pspA mRNA in Streptococcus pneumoniae.Nucleic acids research · 2026Article
- Host-pathogen interaction in community-acquired pneumonia: a focus on the immune response.Frontiers in cellular and infection microbiology · 2026Review
- Single cell analysis of diverse immune cell in pneumococcal meningitis.Scientific reports · 2025Article
- C1q Binds to CD4+ T Cells and Inhibits the Release of Pro-Inflammatory Cytokines: Role in the Pathogenesis of Systemic Lupus Erythematosus.International journal of molecular sciences · 2025Article
- Splenic red pulp macrophages eliminate the liver-resistantScience advances · 2025Article
- Intranasal influenza-vectored vaccine expressing pneumococcal surface protein A protects against Influenza and Streptococcus pneumoniae infections.NPJ vaccines · 2024Article
- The complement system: A key player in the host response to infections.European journal of immunology · 2024Review
- Single missense mutations in Vi capsule synthesis genes confer hypervirulence to Salmonella Typhi.Nature communications · 2024Article
- Re-visiting humoral constitutive antibacterial heterogeneity in bloodstream infections.The Lancet. Infectious diseases · 2024Review
- The Activation of JAK/STAT3 Signaling and the Complement System Modulate Inflammation in the Primary Human Dermal Fibroblasts of PXE Patients.Biomedicines · 2023Article
- Hospitalisation outcomes in pneumococcal-vaccinatedERJ open research · 2023Article
- Article
- Lung epithelial cell-derived C3 protects against pneumonia-induced lung injury.Science immunology · 2023Article
- Characterization of the innate immune response to Streptococcus pneumoniae infection in zebrafish.PLoS genetics · 2023Article
- Article
- IgM anti-ACE2 autoantibodies in severe COVID-19 activate complement and perturb vascular endothelial function.JCI insight · 2022Article
- Novel Evidence That Alternative Pathway of Complement Cascade Activation is Required for Optimal Homing and Engraftment of Hematopoietic Stem/progenitor Cells.Stem cell reviews and reports · 2022Article
- Corrected and Republished from: "A Novel, Multiple-Antigen Pneumococcal Vaccine Protects against LethalInfection and immunity · 2022Article
117 more citing papers are in PubMed but not listed here.
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8 authors.
Funding
No grant is acknowledged in the PubMed record.
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.
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