title: Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes.
abstract: The role of IgA in the control of invasive mucosal pathogens such as Streptococcus pneumoniae is poorly understood. We demonstrate that human pneumococcal capsular polysaccharide-specific IgA initiated dose-dependent killing of S. pneumoniae with complement and phagocytes. The majority of specific IgA in serum was of the polymeric form (pIgA), and the efficiency of pIgA-initiated killing exceeded that of monomeric IgA-initiated killing. In the absence of complement, specific IgA induced minimal bacterial adherence, uptake, and killing. Killing of S. pneumoniae by resting phagocytes with immune IgA required complement, predominantly via the C2-independent alternative pathway, which requires factor B, but not calcium. Both S. pneumoniae-bound IgA and complement were involved, as demonstrated by a 50% decrease in killing with blocking of Fcalpha receptor (CD89) and CR1/CR3 (CD35/CD11b). However, IgA-mediated killing by phagocytes could be reproduced in the absence of opsonic complement by pre-activating phagocytes with the inflammatory products C5a and TNF-alpha. Thus, S. pneumoniae capsule-specific IgA may show distinct roles in effecting clearance of S. pneumoniae in the presence or absence of inflammation. These data suggest mechanisms whereby pIgA may serve to control pneumococcal infections locally and upon the pathogen's entry into the bloodstream.
authors.affiliation: Infectious Disease Section, Department of Medicine, Veterans Affairs Medical Center and University of Minnesota Medical School, Minneapolis, Minnesota 55417, USA. janof001@tc.umn.edu
authors.forename: E N
authors.initials: EN
authors.lastname: Janoff
authors.forename: C
authors.initials: C
authors.lastname: Fasching
authors.forename: J M
authors.initials: JM
authors.lastname: Orenstein
authors.forename: J B
authors.initials: JB
authors.lastname: Rubins
authors.forename: N L
authors.initials: NL
authors.lastname: Opstad
authors.forename: A P
authors.initials: AP
authors.lastname: Dalmasso
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000276:immunology*; D016667:Bacterial Capsules / Q000276:immunology*; D001428:Bacterial Vaccines / Q000276:immunology*; D001770:Blood Bactericidal Activity; D003165:Complement System Proteins / Q000502:physiology*; D005260:Female; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000502:physiology; D008297:Male; D009504:Neutrophils / Q000276:immunology; D010586:Phagocytes / Q000502:physiology*; D022242:Pneumococcal Vaccines; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D007070:Immunoglobulin A; D016177:Macrophage-1 Antigen; D022242:Pneumococcal Vaccines; C034639:polymeric IgA; D003165:Complement System Proteins