Please use this identifier to cite or link to this item: http://hdl.handle.net/1959.13/932136

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Title
Chlamydial respiratory infection during allergen sensitization drives neutrophilic allergic airways disease
Author/Creator
Horvat, Jay C.;  Starkey, Malcolm R.;  Kim, Richard Y.;  Beagley, Kenneth W.;  Preston, Julie A.;  Gibson, Peter G.;  Foster, Paul S.;  Hansbro, Philip M.
Institution
The University of Newcastle. Faculty of Health, School of Biomedical Sciences and Pharmacy
Description
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-γ release from T cells. The phenotype of suppressed but persistent Th2 responses in association with enhanced neutrophilia is reminiscent of eutrophilic 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-γ production and reversed the suppressive effects on mucussecreting 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-γ 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.
Relation
Journal of Immunology Vol. 184, Issue 8, p. 4159-4169
Publisher Link
http://dx.doi.org/10.4049/jimmunol.0902287
Date
2010
Publisher
American Association of Immunologists
Keyword(s)
neutrophilic asthma;  airways hyperresponsiveness (AHR);  allergic airways disease (AAD);  chlamydial infection
Resource Type
journal article
Identifier
http://hdl.handle.net/1959.13/932136
Identifier
ISSN:0022-1767
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Subject
"Journal of Immunology"
 
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