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PMID: 10525053 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

Killing of Streptococcus pneumoniae by capsular polysaccharide-specific polymeric IgA, complement, and phagocytes.

The Journal of clinical investigation ·Vol. 104 ·No. 8 ·1999-10-00 ·Pages 1139-47

Janoff EN, Fasching C, Orenstein JM, Rubins JB, Opstad NL, Dalmasso AP

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.

MeSH Terms
Adult Antibodies, Bacterial/immunology Bacterial Capsules/immunology Bacterial Vaccines/immunology Blood Bactericidal Activity Complement System Proteins/physiology Female Humans Immunoglobulin A/immunology Macrophage-1 Antigen/physiology Male Neutrophils/immunology Phagocytes/physiology Pneumococcal Vaccines Streptococcus pneumoniae/immunology
Chemicals
Antibodies, Bacterial Bacterial Vaccines Immunoglobulin A Macrophage-1 Antigen Pneumococcal Vaccines polymeric IgA Complement System Proteins
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Janoff E N
Infectious Disease Section, Department of Medicine, Veterans Affairs Medical Center and University of Minnesota Medical School, Minneapolis, Minnesota 55417, USA. janof001@tc.umn.edu
Fasching C
Orenstein J M
Rubins J B
Opstad N L
Dalmasso A P
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI6310
Email
janof001@tc.umn.edu
Published
1999-10-00
Pages
1139-47
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC408571
Subset
IM
Grants
NIAID NIH HHS · AI-042240 · United States
NIAID NIH HHS · AI-31373 · United States
NIAID NIH HHS · AI-39445 · United States
External Links
PubMed source DOI: 10.1172/JCI6310 PMC Full Text View journal details
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