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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 2

Major pneumococcal surface proteins interacting with human mucus proteins.

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Major pneumococcal surface proteins interacting with human mucus protein...
(A–C) Gradient SDS-PAGE (4%–12%) and Western blot of purified mucosal proteins lactoferrin (LF), sIgA, lysozyme (Lyz), and hNF (each 1 μg). Proteins in hNF were detected using a specific polyclonal rabbit anti–human lactoferrin antibody (A), an alkaline phosphatase–coupled goat anti-human IgA antibody (B), or a rabbit anti–human lysozyme antibody (C). Protein band at 62 kDa likely represents albumin. Lane M, SeeBlue Plus2 Pre-Stained Standard (Thermo Fisher Scientific). (D) Acquisition of soluble LF, sIgA, and IgG from hNF by Spn. Bacteria (5 × 106 CFU per 50 μL) were incubated with 50 μg/mL of hNF. Binding of bacteria-associated LF, sIgA, and IgG was analyzed by flow cytometry. The percentage binding of at least 3 independent experiments is shown as mean values with error bars ± SD. ***P < 0.001, ****P < 0.0001 by 1-way ANOVA followed by Tukey’s multiple comparison, n = 6–10.
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