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Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1
Ulrike Binsker, … , Alexandria J. Hammond, Jeffrey N. Weiser
Ulrike Binsker, … , Alexandria J. Hammond, Jeffrey N. Weiser
Published November 5, 2019
Citation Information: J Clin Invest. 2020;130(2):927-941. https://doi.org/10.1172/JCI132005.
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Research Article Microbiology

Immune exclusion by naturally acquired secretory IgA against pneumococcal pilus-1

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Abstract

Successful infection by mucosal pathogens requires overcoming the mucus barrier. To better understand this key step, we performed a survey of the interactions between human respiratory mucus and the human pathogen Streptococcus pneumoniae. Pneumococcal adherence to adult human nasal fluid was seen only by isolates expressing pilus-1. Robust binding was independent of pilus-1 adhesive properties but required Fab-dependent recognition of RrgB, the pilus shaft protein, by naturally acquired secretory IgA (sIgA). Pilus-1 binding by specific sIgA led to bacterial agglutination, but adherence required interaction of agglutinated pneumococci and entrapment in mucus particles. To test the effect of these interactions in vivo, pneumococci were preincubated with human sIgA before intranasal challenge in a mouse model of colonization. sIgA treatment resulted in rapid immune exclusion of pilus-expressing pneumococci. Our findings predict that immune exclusion would select for nonpiliated isolates in individuals who acquired RrgB-specific sIgA from prior episodes of colonization with piliated strains. Accordingly, genomic data comparing isolates carried by mothers and their children showed that mothers are less likely to be colonized with pilus-expressing strains. Our study provides a specific example of immune exclusion involving naturally acquired antibody in the human host, a major factor driving pneumococcal adaptation.

Authors

Ulrike Binsker, John A. Lees, Alexandria J. Hammond, Jeffrey N. Weiser

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Figure 1

Mucosal protein–mediated binding of Spn to human nasal fluid.

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Mucosal protein–mediated binding of Spn to human nasal fluid.
(A–D) Adhe...
(A–D) Adherence of Spn TIGR4 to human nasal fluid (hNF) was analyzed in a solid-phase assay. (A) Bacteria (1 × 104) in 100 μL DMEM were incubated with 10 μg immobilized bovine submaxillary mucus (BM) or hNF in the presence or absence of 0.1% BSA for 2 hours at 30°C. Bound bacteria were determined by resuspension with 0.001% Triton X-100 following plating on TS agar plates supplemented with 200 μg/mL streptomycin. (B) Adherence of TIGR4 and TIGR4Δcps (each 1 × 104 per 100 μL) to hNF. (C) Treatment of immobilized hNF with 100 mM NaIO4 in 50 mM sodium acetate buffer for 30 minutes at 4°C in the dark followed by blocking with 0.1% BSA and incubation with 2 × 104 Spn TIGR4. (D) Immobilized hNF was incubated with increasing concentrations of trypsin with or without protease inhibitor (PI) for 30 minutes at 37°C followed by incubation of 0.1% BSA and 2 × 104 Spn TIGR4 in 100 μL DMEM for 2 hours at 30°C. Experiments were performed in duplicate, and mean values of 3 independent experiments are shown with error bars corresponding to SD. **P < 0.01, ****P < 0.0001 by 2-tailed unpaired t test, n = 6 (A, B, and D), or 1-way ANOVA followed by Dunnett’s multiple comparison, n = 6 (C).

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