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

Caroline M Weight,Robert S Heyderman,Simon P Jochems,Jesús Reiné,Cristina Venturini,Jeremy S Brown,Daniela M Ferreira,Sherin Pojar,Mahdad Noursadeghi,Carla Solórzano,Elissavet Nikolaou

doi:10.1038/s41467-019-11005-2

Caroline M Weight, Robert S Heyderman + Show 9 more

Open Access

https://doi.org/10.1038/s41467-019-11005-2

Copy DOI

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.

Highlights

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
Our data suggest that pneumococcal engagement with the epithelium in the early phases of colonisation may occur without eliciting a marked host response, but as colonisation becomes more established, epithelial sensing of S. pneumoniae enhances innate immunity/inflammation which we propose promotes clearance
Clearance was defined as when S. pneumoniae colonisation became negative by culture of nasal wash

Summary

Introduction

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. 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. The relative importance of epithelial endocytosis and paracellular migration in colonisation and invasion remains uncertain[16], but could influence epithelial sensing of this otherwise extracellular pathogen[14]. For example this may include Nod[1] signalling via peptidoglycan[17] and TLR4 signalling via pneumolysin, a poreforming toxin that induces inflammation and mediates both clearance and transmission in an infant mouse model[18,19,20]

Methods

Results

Conclusion