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https://hdl.handle.net/2440/87084
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Type: | Journal article |
Title: | Development of primary invasive pneumococcal disease caused by serotype 1 pneumococci is driven by early increased type I interferon response in the lung |
Author: | Hughes, C. Harvey, R. Plumptre, C. Paton, J. |
Citation: | Infection and Immunity, 2014; 82(9):3919-3926 |
Publisher: | American Society for Microbiology |
Issue Date: | 2014 |
ISSN: | 0019-9567 1098-5522 |
Editor: | Pirofski, L. |
Statement of Responsibility: | Catherine E. Hughes, Richard M. Harvey, Charles D. Plumptre and James C. Paton |
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. |
Keywords: | Pleural Cavity Lung Animals Mice Streptococcus pneumoniae Bacteremia Pneumococcal Infections Interferon Type I Antibodies, Bacterial Female Antibodies, Neutralizing |
Description: | Published ahead of print 7 July 2014 |
Rights: | © 2014, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/IAI.02067-14 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/565526 http://purl.org/au-research/grants/arc/DP120101432 |
Published version: | http://dx.doi.org/10.1128/iai.02067-14 |
Appears in Collections: | Aurora harvest 7 Molecular and Biomedical Science publications |
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