Eosinophils, eosinophil ribonucleases, and their role in host defense against respiratory virus pathogens

Eosinophils remain among the most enigmatic of cells, as our appreciation of their detrimental activities—e.g., asthma and allergic disease—far outweighs our understanding of their beneficial effects. Among the major secretory effector proteins of eosinophils are the ribonucleases eosinophil‐derived neurotoxin (EDN) and eosinophil cationic protein (ECP) in primates and their orthologs, the eosinophil‐associated ribonucleases (EARs) in rodents. The rapid diversification observed among these ribonucleases suggested that the ultimate target(s) might be similarly efficient at generating sequence diversity while maintaining an unalterable susceptibility to ribonucleolytic cleavage. This has prompted us to consider a role for these proteins and by extension, for eosinophils, in host defense against single‐stranded RNA virus pathogens. We detail our studies of the antiviral activity of eosinophils and eosinophil ribonucleases against respiratory syncytial virus (RSV) in vitro and the related, natural rodent pathogen, pneumonia virus of mice (PVM), in vivo, and consider the possibility that antiviral host defense and the dysregulated responses leading to asthma represent opposing sides of an eosinophil‐mediated double‐edged sword.