Dual RNA-seq in Streptococcus pneumoniae infection reveals compartmentalized neutrophil responses in lung and pleural space

Ritchie, N. D. and Evans, T. (2019) Dual RNA-seq in Streptococcus pneumoniae infection reveals compartmentalized neutrophil responses in lung and pleural space. mSystems, 4(4), e00216-19. (doi: 10.1128/mSystems.00216-19) (PMID:31409659) (PMCID:PMC6697439)

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Abstract

Streptococcus pneumoniae is the dominant cause of community-acquired pneumonia worldwide. Invasion of the pleural space is common and results in increased mortality. We set out to determine the bacterial and host factors that influence invasion of the pleural space. In a murine model of pneumococcal infection, we isolated neutrophil-dominated samples of bronchoalveolar and pleural fluid containing bacteria 48 hours after infection. Using dual RNA sequencing (RNA-seq), we characterized bacterial and host transcripts that were differentially regulated between these compartments and bacteria in broth and resting neutrophils, respectively. Pleural and lung samples showed upregulation of genes involved in the positive regulation of neutrophil extravasation but downregulation of genes mediating bacterial killing. Compared to the lung samples, cells within the pleural space showed marked upregulation of many genes induced by type I interferons, which are cytokines implicated in preventing bacterial transmigration across epithelial barriers. Differences in the bacterial transcripts between the infected samples and bacteria grown in broth showed the upregulation of genes in the bacteriocin locus, the pneumococcal surface adhesin PsaA, and the glycopeptide resistance gene vanZ; the gene encoding the ClpP protease was downregulated in infection. One hundred sixty-nine intergenic putative small bacterial RNAs were also identified, of which 43 (25.4%) small RNAs had been previously described. Forty-two of the small RNAs were upregulated in pleura compared to broth, including many previously identified as being important in virulence. Our results have identified key host and bacterial responses to invasion of the pleural space that can be potentially exploited to develop alternative antimicrobial strategies for the prevention and treatment of pneumococcal pleural disease.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ritchie, Dr Neil and Evans, Professor Tom
Authors: Ritchie, N. D., and Evans, T.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:mSystems
Publisher:American Society for Microbiology
ISSN:2379-5077
ISSN (Online):2379-5077
Published Online:13 August 2019
Copyright Holders:Copyright © 2019 Ritchie and Evans.
First Published:First published in mSystems 4(4):e00216-19
Publisher Policy:Reproduced under a Creative Commons license

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
559131The role of Th17 immunity in pneumococcal diseaseTom EvansMedical Research Council (MRC)G1001998III - BACTERIOLOGY