Pulmonary eosinophilia and production of MIP-1 alpha are prominent responses to infection with pneumonia virus of mice

Human eosinophils secrete two distinct ribonucleases that have antiviral ac tivity against pathogens of the family Paramyxoviridae. To examine the role of eosinophils and their ribonucleases in host defense against paramyxovir us pathogens in vivo we have developed a mouse model involving a viral path ogen that naturally targets a rodent host. In this work we describe infecti on of Balb/c mice with pneumonia virus of mice (PVM, strain J3666), a param yxovirus pathogen found frequently among rodent populations. We show here t hat pulmonary eosinophilia is an immediate response to infection with PVM, with bronchoalveolar lavage fluid containing 12-14% eosinophils obtained as early as day 3 postinoculation, Infection is accompanied by the production of macrophage inflammatory protein-1-alpha (MIP-1 alpha), a chemokine that has been associated with the pulmonary eosinophilia observed in response t o respiratory syncytial virus infection in humans and with enhanced clear a nce of influenza virus in mice. Interestingly, we observed no changes in ex pression of the chemoattractants eotaxin and RANTES in response to PVM infe ction, and interleukin-5 remained undetectable throughout. These responses- clinical pathology, viral recovery, pulmonary eosinophilia, and production of MIP-1 alpha-will provide a means for exploring the role of eosinophils, eosinophil secretory ribonucleases, and eosinophil chemoattractants in host defense against PVM and related paramyxovirus pathogens in vivo. (C) 2000 Academic Press.