Killing of Streptococcus pneumoniae by capsular polysaccharide–specific polymeric IgA, complement, and phagocytes
Edward N. Janoff, … , Nancy L. Opstad, Agustin P. Dalmasso
Edward N. Janoff, … , Nancy L. Opstad, Agustin P. Dalmasso
Published October 15, 1999
Citation Information: J Clin Invest. 1999;104(8):1139-1147. https://doi.org/10.1172/JCI6310.
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Article

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 Fcα 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-α. 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

Edward N. Janoff, Claudine Fasching, Jan M. Orenstein, Jeffrey B. Rubins, Nancy L. Opstad, Agustin P. Dalmasso

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Figure 1

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(a) Distribution of molecular forms of IgA (mIgA and pIgA) in immune ser...
(a) Distribution of molecular forms of IgA (mIgA and pIgA) in immune serum for type 14 PPS–specific IgA (black circles; solid lines) and total serum IgA (open circles; dotted line) by gel filtration (mean of 2 experiments). Optical density (OD) represents absorbance at 405 nm by ELISA for type 14–specific IgA and absorbance at 280 nm for total serum IgA (0.2 AUFS absorbance units, full scale); the latter represents approximately 1,000-fold more protein than the former (2 μg/mL type 14–specific IgA and 2 mg/mL total IgA). Type 14–specific IgA comprised 1.2% of pIgA and 0.15% of mIgA. Vertical lines represent peaks of pIgA and mIgA standards. (b) Nondenaturing PAGE of purified IgA before and after size fractionation by gel filtration. Lane 1: purified IgA from serum sample before separation; lane 2: IgA standard containing both pIgA and mIgA; lane 3: purified pIga fraction pool; lane 4: purified mIgA pool.