title: Allergic airway inflammation disrupts interleukin-17 mediated host defense against streptococcus pneumoniae infection.
abstract: Despite decreasing rates of invasive pneumococcal disease caused by vaccine serotypes, the prevalence of invasive pneumococcal pneumonia in asthmatic patients remains high. However, little is known about the mechanisms underlying the susceptibility of the asthmatic airway to bacterial infections. In this study, we used a combined model of allergic airway inflammation and Streptococcus pneumoniae lung infection to investigate the association between persistent allergic inflammation in the airway and antibacterial host defenses against S. pneumoniae. When challenged with S. pneumoniae, allergic mice exhibited higher airway bacterial burdens, greater eosinophil infiltration, lower neutrophil infiltration, and more severe structural damage than non-allergic mice. In sensitized mice, S. pneumoniae infection elicited higher IL-4 but lower IFN-γ, IL-17 and defensin-β2 expression than in control mice. These results indicate that persistent allergic inflammation impaired airway host defense against S. pneumoniae is associated with the insufficient IL-17 responses. To elicit IL-17 induced-anti-bacterial immune responses, mice were intranasally immunized with rIL-17. Immunized mice exhibited fewer bacterial colonies in the respiratory tract and less severe lung pathology than unimmunized mice. rIL-17 contributed to airway host defense enhancement and innate immune response promotion, which was associated with increased IL-23, MIP-2 and defensin-β2 expression. Administration of exogenous IL-17 (2 μg/mouse) suppressed eosinophil-related immune responses. The results demonstrate IL-17 plays a key role in host defenses against bacterial infection in allergic airways and suggest that exogenous IL-17 administration promotes the anti-becterial immune responses and attenuates the existed allergic inflammation.
authors.affiliation: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China; Department of Sciences and Education, Shanghai Jiao Tong University Affiliated Children's Hospital, Shanghai 200062, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Guo
authors.affiliation: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Liang-Xia
authors.initials: LX
authors.lastname: Wu
authors.affiliation: Department of Molecular Biosciences & Bioengineering, University of Hawaii-Manoa, Honolulu, HI 96822, USA.
authors.forename: Can-Xin
authors.initials: CX
authors.lastname: Jones
authors.affiliation: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Chun-Li
authors.initials: CL
authors.lastname: Hao
authors.affiliation: Department of Sciences and Education, Shanghai Jiao Tong University Affiliated Children's Hospital, Shanghai 200062, China. Electronic address: hel@shchildren.com.cn.
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.affiliation: Department of Pediatrics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: jhuazhang@yeah.net.
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D004195:Disease Models, Animal; D004804:Eosinophils / Q000276:immunology*; D005260:Female; D006801:Humans; D006967:Hypersensitivity / Q000150:complications / Q000276:immunology*; D007113:Immunity, Innate; D020381:Interleukin-17 / Q000008:administration & dosage*; D008168:Lung / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009504:Neutrophils / Q000276:immunology*; D011008:Pneumococcal Infections / Q000150:complications / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*
chemical_list: D020381:Interleukin-17
keywords: Airway inflammation; Allergy; Interleukin-17; Streptococcus pneumoniae