Chlamydial Respiratory Infection during Allergen Sensitization Drives Neutrophilic Allergic Airways Disease

被引:70
作者
Horvat, Jay C. [1 ,2 ]
Starkey, Malcolm R. [1 ,2 ]
Kim, Richard Y. [1 ,2 ]
Beagley, Kenneth W. [1 ,2 ,3 ]
Preston, Julie A. [1 ,2 ]
Gibson, Peter G. [1 ,2 ]
Foster, Paul S. [1 ,2 ]
Hansbro, Philip M. [1 ,2 ]
机构
[1] Univ Newcastle, Ctr Asthma & Resp Dis, Newcastle, NSW 2300, Australia
[2] Univ Newcastle, Hunter Med Res Inst, Newcastle, NSW 2300, Australia
[3] Queensland Univ Technol, Inst Hlth & Biomed Innovat, Brisbane, Qld 4001, Australia
基金
英国医学研究理事会;
关键词
T-CELL RESPONSES; ANTIGEN-PRESENTING CELLS; DENDRITIC CELLS; SEVERE ASTHMA; INFLAMMATORY SUBTYPES; PNEUMONIAE INFECTION; BACTERIAL-INFECTION; MESSENGER-RNA; IMMUNE-SYSTEM; MICE SHOW;
D O I
10.4049/jimmunol.0902287
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Neutrophilic asthma is a prevalent, yet recently described phenotype of asthma. It is characterized by neutrophilic rather than eosinophilic airway inflammation and airways hyperresponsiveness (AHR) and may have an infectious origin. Chlamydial respiratory infections are associated with asthma, but how these Th1-inducing bacteria influence Th2-mediated asthma remains unknown. The effects of chlamydial infection on the development of asthma were investigated using a BALB/c mouse model of OVA-induced allergic airways disease (AAD). The effects of current and resolved Chlamydia muridarum infection during OVA sensitization on AAD were assessed and compared with uninfected and nonsensitized controls. Current, but not resolved, infection attenuated hallmark features of AAD: pulmonary eosinophil influx, T cell production of IL-5, mucus-secreting cell hyperplasia, and AHR. Current infection also induced robust OVA-driven neutrophilic inflammation and IFN-gamma release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of neutrophilic asthma. This phenotype was also characterized by increased pulmonary IL-12 and IL-17 expression and activation of APCs, as well as by reduced thymus- and activation-regulated chemokine. Inhibition of pulmonary neutrophil influx during infection blocked OVA-induced neutrophilic inflammation and T cell IFN-gamma production and reversed the suppressive effects on mucus-secreting cell hyperplasia and AHR during AAD. These changes correlated with decreased IL-12 and IL-17 expression, increased thymus- and activation-regulated chemokine and altered APC activation. Blocking IFN-gamma and IL-17 during OVA challenge had no effect. Thus, active chlamydial respiratory infection during sensitization enhances subsequent neutrophilic inflammation and Th1/Th17 responses during allergen exposure and may have a role in the pathogenesis of neutrophilic asthma. The Journal of Immunology, 2010, 184: 4159-4169.
引用
收藏
页码:4159 / 4169
页数:11
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