Antigen-Independent Restriction of Pneumococcal Density by Mucosal Adjuvant Cholera Toxin Subunit B

Kirsten Kuipers, Dimitri A. Diavatopoulos, Fred van Opzeeland, Elles Simonetti, Corne H. van den Kieboom, Mariska Kerstholt, Malgorzata Borczyk, D. van IngenSchenau, Eelke T. Brandsma, Mihai G. Netea, Marien I. de Jonge*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    12 Citations (Scopus)

    Abstract

    For many bacterial respiratory infections, development of (severe) disease is preceded by asymptomatic colonization of the upper airways. For Streptococcus pneumoniae, the transition to severe lower respiratory tract infection is associated with an increase in nasopharyngeal colonization density. Insight into how the mucosal immune system restricts colonization may provide new strategies to prevent clinical symptoms. Several studies have provided indirect evidence that the mucosal adjuvant cholera toxin subunit B (CTB) may confer nonspecific protection against respiratory infections. Here, we show that CTB reduces the pneumococcal load in the nasopharynx, which required activation of the caspase-1/11 inflammasome, mucosal T cells, and macrophages. Our findings suggest that CTB-dependent activation of the local innate response synergizes with noncognate T cells to restrict bacterial load. Our study not only provides insight into the immunological components required for containment and clearance of pneumococcal carriage, but also highlights an important yet often understudied aspect of adjuvants.

    Original languageEnglish
    Pages (from-to)1588-1596
    Number of pages9
    JournalThe Journal of Infectious Diseases
    Volume214
    Issue number10
    DOIs
    Publication statusPublished - 15-Nov-2016

    Keywords

    • cholera toxin subunit B
    • mucosal adjuvant
    • Streptococcus pneumoniae
    • bacterial colonization
    • bacterial density
    • inflammasome
    • T cells
    • macrophages
    • MEMORY T-CELLS
    • INFLUENZA VACCINE
    • INNATE IMMUNITY
    • MICE
    • ACTIVATION
    • INFLAMMASOMES
    • COLONIZATION
    • INDUCTION
    • ORGANS
    • TH1

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