- Title
- CCL7 and IRF-7 mediate hallmark inflammatory and IFN responses following rhinovirus 1B infection
- Creator
- Girkin, Jason; Hatchwell, Luke; Foster, Paul; Johnston, Sebastian L.; Bartlett, Nathan; Collison, Adam; Mattes, Joerg
- Relation
- NHMRC.130093
- Relation
- Journal of Immunology Vol. 194, Issue 10, p. 4924-4930
- Publisher Link
- http://dx.doi.org/10.4049/jimmunol.1401362
- Publisher
- American Association of Immunologists
- Resource Type
- journal article
- Date
- 2015
- Description
- Rhinovirus (RV) infections are common and have the potential to exacerbate asthma. We have determined the lung transcriptome in RV strain 1B-infected naive BALB/c mice (nonallergic) and identified CCL7 and IFN regulatory factor (IRF)-7 among the most upregulated mRNA transcripts in the lung. To investigate their roles we employed anti-CCL7 Abs and an IRF-7-targeting small interfering RNA in vivo. Neutralizing CCL7 or inhibiting IRF-7 limited neutrophil and macrophage influx and IFN responses in nonallergic mice. Neutralizing CCL7 also reduced activation of NF-κB p65 and p50 subunits, as well as airway hyperreactivity (AHR) in nonallergic mice. However, neither NF-κB subunit activation nor AHR was abolished with infection of allergic mice after neutralizing CCL7, despite a reduction in the number of neutrophils, macrophages, and eosinophils. IRF-7 small interfering RNA primarily suppressed IFN-α and IFN-β levels during infection of allergic mice. Our data highlight a pivotal role of CCL7 and IRF-7 in RV-induced inflammation and IFN responses and link NF-κB signaling to the development of AHR.
- Subject
- rhinovirus infections; asthma; lung transcriptome; CCL7; IRF-7
- Identifier
- http://hdl.handle.net/1959.13/1311157
- Identifier
- uon:22160
- Identifier
- ISSN:0022-1767
- Language
- eng
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