Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa (original) (raw)

Bayes, Hannah K., Ritchie, Neil D. and Evans, Thomas J. ORCID: https://orcid.org/0000-0002-4140-6352(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)

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.

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Funder and Project Information

1

The Proinflammatory Th17 Response as a Therapeutic Target in Cystic Fibrosis Lung Disease

Tom Evans

094779/Z/10/Z

III - BACTERIOLOGY

1

The role of Th17 immunity in pneumococcal disease

Tom Evans

G1001998

III - BACTERIOLOGY

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