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

Weight, Caroline M, Venturini, Cristina, Pojar, Sherin ORCID: https://orcid.org/0000-0002-7746-3279, Jochems, Simon ORCID: https://orcid.org/0000-0002-4835-1032, Reiné, Jesús, Nikolaou, Elissavet, SolorzanoGonzalez, Carla, Noursadeghi, Mahdad, Brown, Jeremy S, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 and Heyderman, Robert S (2019) 'Microinvasion by Streptococcus pneumoniae induces epithelial innate immunity during colonisation at the human mucosal surface.'. Nature Communications, Vol 10, Issue 1, e3060.

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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.

Item Type:	Article
Subjects:	QS Anatomy > Histology > QS 532 Types of normal tissue QS Anatomy > Histology > QS 532.5 Specific types of tissue QW Microbiology and Immunology > Immunity by Type > QW 563 Local immunity WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1038/s41467-019-11005-2
Depositing User:	Stacy Murtagh
Date Deposited:	19 Jul 2019 08:42
Last Modified:	05 Nov 2019 14:57
URI:	https://archive.lstmed.ac.uk/id/eprint/11240

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