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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Effect of depletion and repletion of selected human complement component...
Effect of depletion and repletion of selected human complement components in human serum on IgA-mediated killing of type 14 S. pneumoniae by IgA. Organisms were incubated with 1 mg/mL of immune IgA, differentiated HL-60 cells, and a complement source consisting of 10% serum from a hypogammaglobulinemic patient, serum depleted of the classical pathway component C2, serum depleted of the alternative pathway component factor B, or serum depleted for factor B and then repleted with a physiologic concentration of factor B (200 μg/mL). All sera were preadsorbed with type 14 pneumococci before the killing assay to remove specific antibody in the complement source. Results are shown as mean ± SEM of 7 experiments. *P < 0.05 vs. normal complement and factor B–repleted complement.