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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 7

Human nasal fluid agglutinates pneumococci in a pilus-dependent manner.

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Human nasal fluid agglutinates pneumococci in a pilus-dependent manner.
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(A and B) WT Spn and the pilus-1–deficient mutant were incubated with hNF (A) or purified human sIgA (B) for 2 hours at 37°C and 5% CO2. Mucus (blue) was stained with Alcian blue, and bacteria (green) were detected using rabbit anti-capsule antibody and secondary FITC-coupled goat anti-rabbit IgG. Agglutination was visualized by microscopy on an Axiovert 40 CFL microscope equipped with an Axiocam IC digital camera. Original magnification ×630. (C) Adherence of Spn to supernatant of centrifuged hNF. Before immobilization, hNF was centrifuged for 5 minutes at 10,000 g; n = 4.
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