Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface

Caroline M. Weight (), Cristina Venturini, Sherin Pojar, Simon P. Jochems, Jesús Reiné, Elissavet Nikolaou, Carla Solórzano, Mahdad Noursadeghi, Jeremy S. Brown, Daniela M. Ferreira and Robert S. Heyderman
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Caroline M. Weight: University College London
Cristina Venturini: University College London
Sherin Pojar: Liverpool School of Tropical Medicine
Simon P. Jochems: Liverpool School of Tropical Medicine
Jesús Reiné: Liverpool School of Tropical Medicine
Elissavet Nikolaou: Liverpool School of Tropical Medicine
Carla Solórzano: Liverpool School of Tropical Medicine
Mahdad Noursadeghi: University College London
Jeremy S. Brown: University College London
Daniela M. Ferreira: Liverpool School of Tropical Medicine
Robert S. Heyderman: University College London

Nature Communications, 2019, vol. 10, issue 1, 1-15

Abstract: Abstract Control of Streptococcus pneumoniae colonisation at human mucosal surfaces is critical to reducing the burden of pneumonia and invasive pneumococcal disease, interrupting transmission, and achieving herd protection. Here, we use an experimental human pneumococcal carriage model (EHPC) to show that S. pneumoniae colonisation is associated with epithelial surface adherence, micro-colony formation and invasion, without overt disease. Interactions between different strains and the epithelium shaped the host transcriptomic response in vitro. Using epithelial modules from a human epithelial cell model that recapitulates our in vivo findings, comprising of innate signalling and regulatory pathways, inflammatory mediators, cellular metabolism and stress response genes, we find that inflammation in the EHPC model is most prominent around the time of bacterial clearance. Our results indicate that, rather than being confined to the epithelial surface and the overlying mucus layer, the pneumococcus undergoes micro-invasion of the epithelium that enhances inflammatory and innate immune responses associated with clearance.

Date: 2019
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DOI: 10.1038/s41467-019-11005-2

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