Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung

Hughes, C. E. , Harvey, R. M., Plumptre, C. D. and Paton, J. C. (2014) Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung. Infection and Immunity, 82(9), pp. 3919-3926. (doi: 10.1128/IAI.02067-14) (PMID:25001606) (PMCID:PMC4187798)

Abstract

The pneumococcus is the world's foremost respiratory pathogen, but the mechanisms allowing this pathogen to proceed from initial asymptomatic colonization to invasive disease are poorly understood. We have examined the early stages of invasive pneumococcal disease (IPD) by comparing host transcriptional responses to an invasive strain and a noninvasive strain of serotype 1 Streptococcus pneumoniae in the mouse lung. While the two strains were present in equal numbers in the lung 6 h after intranasal challenge, only the invasive strain (strain 1861) had invaded the pleural cavity at that time point; this correlated with subsequent development of bacteremia in mice challenged with strain 1861 but not the noninvasive strain (strain 1). Progression beyond the lung was associated with stronger induction of the type I interferon (IFN-I) response in the lung at 6 h. Suppression of the IFN-I response through administration of neutralizing antibody to IFNAR1 (the receptor for type I interferons) led to significantly reduced invasion of the pleural cavity by strain 1861 at 6 h postchallenge. Our data suggest that strong induction of the IFN-I response is a key factor in early progression of invasive serotype 1 strain 1861 beyond the lung during development of IPD.

• Item Type: Articles
• Additional Information: This work was supported by Program Grant 565526 from the National Health and Medical Research Council (NHMRC) of Australia (to J.C.P.) and Discovery Project Grant DP120101432 from the Australian Research Council (to J.C.P.). J.C.P. is a NHMRC Senior Principal Research Fellow.
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Hughes, Dr Catherine
• Authors: Hughes, C. E., Harvey, R. M., Plumptre, C. D., and Paton, J. C.
• College/School: College of Medical Veterinary and Life Sciences > School of Infection & Immunity
• Journal Name: Infection and Immunity
• Publisher: American Society for Microbiology
• ISSN: 0019-9567
• ISSN (Online): 1098-5522
• Published Online: 07 July 2014
• Copyright Holders: Copyright © 2014 American Society for Microbiology
• First Published: First published in Infection and Immunity 82(9):3919-3926
• Publisher Policy: Reproduced in accordance with the copyright policy of the publisher