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 5

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Effect of cation chelators on phagocytic killing of type 14 S. pneumonia...
Effect of cation chelators on phagocytic killing of type 14 S. pneumoniae by IgA in the presence of baby rabbit complement (a) and human complement (b). EDTA, which blocks both alternative and classical pathways, and MgEGTA, which blocks only the classical pathway, were added to killing reactions to determine the complement activation pathway involved in IgA-mediated phagocytic killing of pneumococci by differentiated HL-60 cells. Chelators (EDTA and MgEGTA) were added at 10 mM. All tests were run in triplicate; results are shown as the mean ± SEM of 6 experiments. *P < 0.05 vs. killing without EDTA. Results were the same whether individual experiments used IgA that was 98% pure (<2% IgM) or 99.9% pure (<0.1% IgM).