IL-17 can be protective or deleterious in murine pneumococcal pneumonia

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
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ritchie, Dr Neil and Bayes, Dr Hannah and Evans, Professor Tom and Ritchie, Mr Ryan and Mitchell, Professor Tim
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 > Institute of Infection Immunity and Inflammation
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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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
559131The role of Th17 immunity in pneumococcal diseaseTom EvansMedical Research Council (MRC)G1001998III - BACTERIOLOGY
558681The Proinflammatory Th17 Response as a Therapeutic Target in Cystic Fibrosis Lung DiseaseTom EvansWellcome Trust (WELLCOTR)094779/Z/10/ZIII - BACTERIOLOGY