MIP-1 alpha is produced but it does not control pulmonary inflammation in response to respiratory syncytial virus infection in mice

The intent of this study was to compare the cellular and biochemical inflam matory responses of mice infected with the paramyxovirus pathogens respirat ory syncytial virus (RSV) and pneumonia virus of mice (PVM), Although RSV i s not a natural pathogen of mice, it has been used extensively in mouse mod els of the human disease, as a limited respiratory infection can be establi shed via intranasal inoculation of virus at high titer. In earlier work, we found that acute infection with the natural rodent pathogen, PVM, elicited a rapid and sustained pulmonary inflammatory response (peak, 1.7 x 10(6) l eukocytes/ml BAL fluid) that was dependent on both local production of MIP- 1 alpha and signaling via its receptor, CCR1. We find here that MIP-1 alpha is also produced in response to RSV, although relatively few leukocytes (< 200 ml BAL fluid) are recruited to the lungs in response. Further experimen ts with CCR1-deficient mice confirm the finding that although MIP-1<alpha> is produced in response to RSV infection, leukocytes do not respond via thi s pathway. Among the explanations for these findings, we propose that there are other, as yet to be identified proinflammatory mediators elicited in r esponse to PVM (but not in response to RSV) that serve to prime the leukocy tes in vivo, thus enabling them to respond to MIP-1 alpha signaling via CCR 1, Furthermore, the differences in disease pathogenesis seen in response to each of these pneumovirus infections in mice raise questions regarding the extent to which primary RSV infection in mice can be used as a model of pr imary RSV infection in humans. (C) 2000 Academic Press.