Eosinophils are enigmatic cells with well-characterized detrimental roles as mediators of allergic diseases and asthma and beneficial features that remain controversial and poorly understood. Indeed, in light of the recent findings that have undermined the hypotheses regarding eosinophils as antiparasitic agents in vivo, it is not at all clear what (if anything) eosinophils do to promote host defense. With this in mind, we have begun to look carefully at some of the intriguing associations that link eosinophils, asthma and allergic bronchospasm, and diseases caused by respiratory viruses, most notably that caused by respiratory syncytial virus (RSV). While eosinophils are associated with bronchospasm and tissue damage, and thus have been uniformly perceived as the villains of RSV disease, we have begun to consider the possibility that eosinophilic inflammation has a """"""""double-edged sword,"""""""" similar to that studied more carefully in neutrophils. Our group has demonstrated that eosinophils can mediate the direct, ribonuclease-dependent reduction in infectivity of RSV in vitro, and that one of the eosinophil secretory proteins, the eosinophil-derived neurotoxin (EDN/ RNase 2), can function alone as an independent antiviral agent. We have extended these findings into an in vivo system using a mouse model of respiratory viral infection. Using a natural rodent pathogen, the pneumovirus pneumonia virus of mice (PVM), we have characterized the inflammatory responses to this infection, and are devising combined antiviral / immunomodulatory strategies as novel therapeutics.
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