Abstract
Background: Respiratory viruses cause asthma exacerbations. Eosinophils are a common inflammatory cell in the airways of many asthmatics and experimentally have been shown to mediate virus-induced airway hyperreactivity. Pulmonary eosinophilia, however, has been associated with reduced virus replication suggesting eosinophils have a role in the lungs' antiviral immune response.
Objective: To determine the effect of eosinophils on parainfluenza virus 1 (PIV-1) infection in the lung.
Methods: PIV-1 replication was evaluated in ovalbumin sensitized and challenged mice, hypereosinophilic (CC10.IL5) transgenic mice and eosinophil-deficient (PHIL) transgenic mice in vivo, and in cultures of isolated human eosinophils.
Results: Mice sensitized and challenged with ovalbumin had reduced quantities of PIV-1 RNA in the lungs 4 days after inoculation compared to nonsensitized mice. Similarly, CC10.IL5 mice with lung hypereosinophilia had reduced PIV-1 RNA compared to wild-type controls, however, this effect was lost in eosinophil-deficient PHIL mice. Human eosinophils inhibited PIV-1 replication in vitro in part through the production of nitric oxide. Eosinophils infected with PIV-1 produced progeny virus, but these virions had minimal infectivity. The reduction in PIV-1 infectivity was not due to PIV-1 RNA degradation by eosinophil-associated RNases.
Conclusions: These results demonstrate a potent antiviral effect of eosinophils that was mediated in part through the production of nitric oxide, but not through the degradation of viral RNA by eosinophil-associated RNases. This potentially beneficial antiviral role for eosinophils should be considered when designing future asthma therapies that target eosinophil depletion.
- Copyright ©ERS 2015