Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa

Bayes, H. K., Ritchie, N. D. and Evans, T. J. (2016) Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa. Infection and Immunity, 84(12), pp. 3507-3516. (doi: 10.1128/IAI.00717-16) (PMID:27698020) (PMCID:PMC5116727)

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Abstract

Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the IL-17 family have been proposed as important in the host response to P. aeruginosa infection through augmenting antibacterial immune responses, although their pro-inflammatory effect may contribute to lung damage that occurs as a result of chronic infection. We set out to explore the role of IL-17 in the host response to chronic P. aeruginosa infection. We used a murine model of chronic pulmonary infection with CF-related strains of P. aeruginosa. We demonstrate that IL-17 cytokine signaling is essential for survival and prevention of chronic infection at 2 weeks post-inoculation using two different P. aeruginosa strains. Following infection, there was a marked expansion of cells within mediastinal lymph nodes, comprised mainly of innate lymphoid cells (ILCs); ∼90% of IL-17 producing cells had markers consistent with Group 3 ILCs. A smaller percentage of IL-17+ cells had markers consistent with a B1 phenotype. In lung homogenates 14 days following infection, there was a significant expansion of IL-17+ cells – about 50% of these were CD3+, split equally between CD4+ Th17 cells and γδ T cells, while the CD3- IL-17+ cells were almost exclusively Group 3 ILCs. Further experiments with B cell deficient mice showed that B cell production of IL-17 or natural antibodies did not provide any defence against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defence against chronic pulmonary infection with P. aeruginosa.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Ritchie, Dr Neil and Bayes, Dr Hannah and Evans, Professor Tom
Authors: Bayes, H. K., Ritchie, N. D., and Evans, T. J.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Infection and Immunity
Publisher:American Society for Microbiology
ISSN:0019-9567
ISSN (Online):1098-5522
Published Online:03 October 2016
Copyright Holders:Copyright © 2016 Bayes et al.
First Published:First published in Infection and Immunity 84(12):3507-3516
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
558681The Proinflammatory Th17 Response as a Therapeutic Target in Cystic Fibrosis Lung DiseaseTom EvansWellcome Trust (WELLCOME)094779/Z/10/ZIII - BACTERIOLOGY
559131The role of Th17 immunity in pneumococcal diseaseTom EvansMedical Research Council (MRC)G1001998III - BACTERIOLOGY