Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens

PLoS Pathogens

Helina Marshall¹  Jeremy S. Brown¹  Win Yan Chan¹  Mark Reglinski¹  Robert Wilson¹  Ricardo J. Jose¹  Helen Baxendale²  Fernanda C. Petersen³  Jonathan M. Cohen⁴  David Goldblatt⁵  Corné de Vogel⁶  Stephen Gordon⁷ 

[1] Centre for Inflammation and Tissue Repair, Division of Medicine, University College Medical School, Rayne Institute, London, United Kingdom;Clinical Immunology Department, Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom;Department of Oral Biology, Faculty of Dentistry, University of Oslo, Norway;Infectious Diseases & Microbiology Unit, UCL Institute of Child Health, London, United Kingdom;Institute of Child Health, University College London, London, United Kingdom;Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands;Respiratory Infection Group, Liverpool School of Tropical Medicine, Liverpool, United Kingdom

关键词: Pneumococcus;    Antigen encapsulation;    Enzyme-linked immunoassays;    Antibodies;    Mouse models;    Antigen processing;    recognition;    Flow cytometry;    Neutrophils;   

DOI  :  10.1371/journal.ppat.1006137

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Naturally acquired immunity against invasive pneumococcal disease (IPD) is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG), representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule.

【 授权许可】

CC BY