The chemokine macrophage-inflammatory protein-1 alpha and its receptor CCR1 control pulmonary inflammation and antiviral host defense in paramyxovirus infection

In this work, we explore the responses of specific gene-deleted mice to inf ection with the paramyxovirus pneumonia virus of mice (PVM), We have shown previously that infection of wild type mice with PVM results in pulmonary n eutrophilia and eosinophilia accompanied by local production of macrophage- inflammatory protein-1 alpha (MIP-1 alpha). Here we examine the role of MIP -1 alpha in the pathogenesis of this disease using mice deficient in MIP-Io or its receptor, CCR1, The inflammatory response to PVM in MIP-1 alpha -de ficient mice was minimal, with similar to 10-60 neutrophils/ml and no eosin ophils detected in bronchoalveolar lavage fluid, Higher levels of infectiou s virus were recovered from lung tissue excised from MIP-1 alpha -deficient than from fully competent mice, suggesting that the inflammatory response limits the rate of virus replication in vivo. PVM infection of CCR1-deficie nt mice was also associated with attenuated Inflammation, with enhanced rec overy of infectious virus, and with accelerated mortality, These results su ggest that the MIP-1 alpha /CCR1-mediated acute inflammatory response prote cts mice by delaying the lethal sequelae of infection.