Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma
dc.contributor.author | Hong, Jun Y | |
dc.contributor.author | Chung, Yutein | |
dc.contributor.author | Steenrod, Jessica | |
dc.contributor.author | Chen, Qiang | |
dc.contributor.author | Lei, Jing | |
dc.contributor.author | Comstock, Adam T | |
dc.contributor.author | Goldsmith, Adam M | |
dc.contributor.author | Bentley, J K | |
dc.contributor.author | Sajjan, Uma S | |
dc.contributor.author | Hershenson, Marc B | |
dc.date.accessioned | 2014-12-08T17:46:35Z | |
dc.date.available | 2014-12-08T17:46:35Z | |
dc.date.issued | 2014-06-07 | |
dc.identifier.citation | Respiratory Research. 2014 Jun 07;15(1):63 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/109511 | en_US |
dc.description.abstract | Abstract Background The mechanisms by which viruses cause asthma exacerbations are not precisely known. Previously, we showed that, in ovalbumin (OVA)-sensitized and -challenged mice with allergic airway inflammation, rhinovirus (RV) infection increases type 2 cytokine production from alternatively-activated (M2) airway macrophages, enhancing eosinophilic inflammation and airways hyperresponsiveness. In this paper, we tested the hypothesis that IL-4 signaling determines the state of macrophage activation and pattern of RV-induced exacerbation in mice with allergic airways disease. Methods Eight week-old wild type or IL-4 receptor knockout (IL-4R KO) mice were sensitized and challenged with OVA and inoculated with RV1B or sham HeLa cell lysate. Results In contrast to OVA-treated wild-type mice with both neutrophilic and eosinophilic airway inflammation, OVA-treated IL-4R KO mice showed increased neutrophilic inflammation with few eosinophils in the airways. Like wild-type mice, IL-4R KO mice showed OVA-induced airway hyperreactivity which was further exacerbated by RV. There was a shift in lung cytokines from a type 2-predominant response to a type 1 response, including production of IL-12p40 and TNF-α. IL-17A was also increased. RV infection of OVA-treated IL-4R KO mice further increased neutrophilic inflammation. Bronchoalveolar macrophages showed an M1 polarization pattern and ex vivo RV infection increased macrophage production of TNF-α, IFN-γ and IL-12p40. Finally, lung cells from OVA-treated IL-4R KO mice showed reduced CD206+ CD301+ M2 macrophages, decreased IL-13 and increased TNF-α and IL-17A production by F4/80+, CD11b+ macrophages. Conclusions OVA-treated IL-4R KO mice show neutrophilic airway inflammation constituting a model of allergic, type 1 cytokine-driven neutrophilic asthma. In the absence of IL-4/IL-13 signaling, RV infection of OVA-treated mice increased type 1 cytokine and IL-17A production from conventionally-activated macrophages, augmenting neutrophilic rather than eosinophilic inflammation. In mice with allergic airways inflammation, IL-4R signaling determines macrophage activation state and the response to subsequent RV infection. | |
dc.title | Macrophage activation state determines the response to rhinovirus infection in a mouse model of allergic asthma | |
dc.type | Article | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/109511/1/12931_2014_Article_1503.pdf | |
dc.identifier.doi | 10.1186/1465-9921-15-63 | en_US |
dc.language.rfc3066 | en | |
dc.rights.holder | Hong et al.; licensee BioMed Central Ltd. | |
dc.date.updated | 2014-12-08T17:46:35Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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