title: MIP-1alpha is produced but it does not control pulmonary inflammation in response to respiratory syncytial virus infection in mice.
abstract: The intent of this study was to compare the cellular and biochemical inflammatory responses of mice infected with the paramyxovirus pathogens respiratory syncytial virus (RSV) and pneumonia virus of mice (PVM). Although RSV is not a natural pathogen of mice, it has been used extensively in mouse models of the human disease, as a limited respiratory infection can be established 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) leukocytes/ml BAL fluid) that was dependent on both local production of MIP-1alpha and signaling via its receptor, CCR1. We find here that MIP-1alpha is also produced in response to RSV, although relatively few leukocytes (<200 ml BAL fluid) are recruited to the lungs in response. Further experiments with CCR1-deficient mice confirm the finding that although MIP-1alpha is produced in response to RSV infection, leukocytes do not respond via this pathway. Among the explanations for these findings, we propose that there are other, as yet to be identified proinflammatory mediators elicited in response to PVM (but not in response to RSV) that serve to prime the leukocytes in vivo, thus enabling them to respond to MIP-1alpha signaling via CCR1. 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 primary RSV infection in humans.
authors.affiliation: Department of Pediatrics, State University of New York Upstate Medical Center, Syracuse, New York 13210, USA.
authors.forename: J B
authors.initials: JB
authors.lastname: Domachowske
authors.forename: C A
authors.initials: CA
authors.lastname: Bonville
authors.forename: J L
authors.initials: JL
authors.lastname: Gao
authors.forename: P M
authors.initials: PM
authors.lastname: Murphy
authors.forename: A J
authors.initials: AJ
authors.lastname: Easton
authors.forename: H F
authors.initials: HF
authors.lastname: Rosenberg
mesh_terms: D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D004195:Disease Models, Animal; D015967:Gene Expression Regulation, Viral; D006801:Humans; D007958:Leukocyte Count; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011024:Pneumonia, Viral / Q000378:metabolism / Q000503:physiopathology*; D018111:Pneumovirus / Q000502:physiology*; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000502:physiology; D018357:Respiratory Syncytial Virus Infections / Q000378:metabolism / Q000503:physiopathology*; D012136:Respiratory Syncytial Viruses / Q000502:physiology*; D013045:Species Specificity; D013047:Specific Pathogen-Free Organisms
chemical_list: C515300:CCR1 protein, human; C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine