Ritchie, N. D., Ritchie, R., Bayes, H. K., Mitchell, T. J. and Evans, T. J. (2018) IL-17 can be protective or deleterious in murine pneumococcal pneumonia. PLoS Pathogens, 14(5), e1007099. (doi: 10.1371/journal.ppat.1007099) (PMID:29813133) (PMCID:PMC5993294)
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Abstract
Streptococcus pneumoniae is the major bacterial cause of community-acquired pneumonia, and the leading agent of childhood pneumonia deaths worldwide. Nasal colonization is an essential step prior to infection. The cytokine IL-17 protects against such colonization and vaccines that enhance IL-17 responses to pneumococcal colonization are being developed. The role of IL-17 in host defence against pneumonia is not known. To address this issue, we have utilized a murine model of pneumococcal pneumonia in which the gene for the IL-17 cytokine family receptor, Il17ra, has been inactivated. Using this model, we show that IL-17 produced predominantly from γδ T cells protects mice against death from the invasive TIGR4 strain (serotype 4) which expresses a relatively thin capsule. However, in pneumonia produced by two heavily encapsulated strains with low invasive potential (serotypes 3 and 6B), IL-17 significantly enhanced mortality. Neutrophil uptake and killing of the serotype 3 strain was significantly impaired compared to the serotype 4 strain and depletion of neutrophils with antibody enhanced survival of mice infected with the highly encapsulated SRL1 strain. These data strongly suggest that IL-17 mediated neutrophil recruitment to the lungs clears infection from the invasive TIGR4 strain but that lung neutrophils exacerbate disease caused by the highly encapsulated pneumococcal strains. Thus, whilst augmenting IL-17 immune responses against pneumococci may decrease nasal colonization, this may worsen outcome during pneumonia caused by some strains.
Item Type: | Articles |
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Status: | Published |
Refereed: | Yes |
Glasgow Author(s) Enlighten ID: | Evans, Professor Tom and Ritchie, Mr Ryan and Ritchie, Dr Neil and Mitchell, Professor Timothy and Bayes, Dr Hannah |
Creator Roles: | Ritchie, N. D.Conceptualization, Formal analysis, Investigation, Methodology, Writing – original draft, Writing – review and editing Ritchie, R.Conceptualization, Investigation, Methodology, Writing – review and editing Bayes, H. K.Formal analysis, Writing – review and editing Mitchell, T. J.Conceptualization, Methodology, Resources, Writing – original draft, Writing – review and editing Evans, T. J.Conceptualization, Formal analysis, Funding acquisition, Investigation, Methodology, Project administration, Resources, Supervision, Writing – original draft, Writing – review and editing |
Authors: | Ritchie, N. D., Ritchie, R., Bayes, H. K., Mitchell, T. J., and Evans, T. J. |
College/School: | College of Medical Veterinary and Life Sciences > School of Infection & Immunity College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing > Dental School |
Journal Name: | PLoS Pathogens |
Publisher: | Public Library of Science |
ISSN: | 1553-7366 |
ISSN (Online): | 1553-7374 |
Copyright Holders: | Copyright © 2018 Ritchie et al. |
First Published: | First published in PLoS Pathogens 14(5): e1007099 |
Publisher Policy: | Reproduced under a Creative Commons License |
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