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 | 2016-12-05T10:10:31Z | |
dc.date.available | 2016-12-05T10:10:31Z | |
dc.date.issued | 2014-06-07 | |
dc.identifier.citation | Respiratory Research. 2014 Jun 07;15(1):63 | |
dc.identifier.uri | http://dx.doi.org/10.1186/1465-9921-15-63 | |
dc.identifier.uri | https://hdl.handle.net/2027.42/134573 | |
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/2027.42/134573/1/12931_2014_Article_1503.pdf | |
dc.language.rfc3066 | en | |
dc.rights.holder | Hong et al.; licensee BioMed Central Ltd. | |
dc.date.updated | 2016-12-05T10:10:32Z | |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
Files in this item
Remediation of Harmful Language
The University of Michigan Library aims to describe library materials in a way that respects the people and communities who create, use, and are represented in our collections. Report harmful or offensive language in catalog records, finding aids, or elsewhere in our collections anonymously through our metadata feedback form. More information at Remediation of Harmful Language.
Accessibility
If you are unable to use this file in its current format, please select the Contact Us link and we can modify it to make it more accessible to you.