title: Antibody-enhanced pneumococcal adherence requires IgA1 protease.
abstract: IgA, the major class of Ig in secretions, classically functions by interfering with microbial attachment to host tissues. Many mucosal pathogens, including Streptococcus pneumoniae, express an IgA1 protease that may circumvent the protective effects of this Ig subclass. Because these proteases are specific for human IgA1, we generated human mAbs to the major surface antigen of the pneumococcus, its capsular polysaccharide, and tested their effect in a colonization model of bacterial adherence to respiratory epithelial cells in culture. Rather than inhibiting adherence, type-specific IgA1 markedly enhanced bacterial attachment to host cells, but only when cleaved by IgA1 protease. Neither antibodies of protease-insensitive subclasses (IgA2 and IgG) nor those directed against heterologous capsules had such activity. The adherence-promoting properties of cleaved antibodies correlated with the cationic characteristics of their variable segments, suggesting that bound Fab fragments may neutralize the inhibitory effect of negatively charged capsules on adhesive interaction with host cells. Coating of pneumococci with anticapsular polysaccharide antibody unmasked the bacterial phosphorylcholine ligand, allowing for increased adherence mediated by binding to the platelet activating factor receptor on epithelial cells. In addition, our findings provide evidence for a novel function of bacterial IgA1 proteases. These enzymes may enable pathogens to subvert the antigen specificity of the humoral immune response to facilitate adhesive interactions and persistence on the mucosal surface.
authors.affiliation: Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA. weiser@mail.med.upenn.edu
authors.forename: Jeffrey N
authors.initials: JN
authors.lastname: Weiser
authors.forename: Deborah
authors.initials: D
authors.lastname: Bae
authors.forename: Claudine
authors.initials: C
authors.lastname: Fasching
authors.forename: Ronald W
authors.initials: RW
authors.lastname: Scamurra
authors.forename: Adam J
authors.initials: AJ
authors.lastname: Ratner
authors.forename: Edward N
authors.initials: EN
authors.lastname: Janoff
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal; D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000276:immunology; D001422:Bacterial Adhesion / Q000276:immunology*; D002478:Cells, Cultured; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D020545:Respiratory Mucosa / Q000276:immunology / Q000382:microbiology; D012697:Serine Endopeptidases / Q000378:metabolism*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D012697:Serine Endopeptidases; C021433:IgA-specific serine endopeptidase