title: Interleukin-17 Is Required for Control of Chronic Lung Infection Caused by Pseudomonas aeruginosa.
abstract: Chronic pulmonary infection with Pseudomonas aeruginosa is a feature of cystic fibrosis (CF) and other chronic lung diseases. Cytokines of the interleukin-17 (IL-17) family have been proposed as important in the host response to P. aeruginosa infection through their role in augmenting antibacterial immune responses, although their proinflammatory 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 mouse survival and prevention of chronic infection at 2 weeks postinoculation 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 (IL-17+) 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 harvested 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 defense against chronic P. aeruginosa infection. Thus, IL-17 rather than antibody is a key element in host defense against chronic pulmonary infection with P. aeruginosa.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Hannah K
authors.initials: HK
authors.lastname: Bayes
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom.
authors.forename: Neil D
authors.initials: ND
authors.lastname: Ritchie
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, United Kingdom tom.evans@glasgow.ac.uk.
authors.forename: Thomas J
authors.identifier: http://orcid.org/0000-0002-4140-6352
authors.initials: TJ
authors.lastname: Evans
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology; D002908:Chronic Disease; D007111:Immunity, Cellular; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008168:Lung / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000378:metabolism* / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000276:immunology / Q000378:metabolism* / Q000382:microbiology*; D011550:Pseudomonas aeruginosa / Q000502:physiology*; D053722:Receptors, Interleukin-17 / Q000235:genetics / Q000378:metabolism
chemical_list: C491673:Il17ra protein, mouse; D020381:Interleukin-17; D053722:Receptors, Interleukin-17