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 infection with the paramyxovirus pneumonia virus of mice (PVM). We have shown previously that infection of wild type mice with PVM results in pulmonary neutrophilia 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-1 alpha or its receptor, CCR1. The inflammatory response to PVM in MIP-1 alpha-deficient mice was minimal, with approximately 10-60 neutrophils/ml and no eosinophils detected in bronchoalveolar lavage fluid. Higher levels of infectious 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-deficient mice was also associated with attenuated inflammation, with enhanced recovery of infectious virus, and with accelerated mortality. These results suggest that the MIP-1 alpha/CCR1-mediated acute inflammatory response protects mice by delaying the lethal sequelae of infection.
Domachowske
J B
JB
Department of Pediatrics, State University of New York Upstate Medical University, Syracuse, NY, USA.
Bonville
C A
CA
Gao
J L
JL
Murphy
P M
PM
Easton
A J
AJ
Rosenberg
H F
HF
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054407:Chemokine CCL4; D004804:Eosinophils / Q000276:immunology / Q000473:pathology / Q000821:virology; D005260:Female; D008168:Lung / Q000276:immunology* / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D019402:Macrophage Inflammatory Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology / Q000473:pathology / Q000821:virology; D018111:Pneumovirus / Q000276:immunology* / Q000302:isolation & purification; D018186:Pneumovirus Infections / Q000276:immunology* / Q000401:mortality / Q000473:pathology* / Q000821:virology; D011657:Pulmonary Eosinophilia / Q000276:immunology / Q000401:mortality / Q000473:pathology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
C515301:Ccr1 protein, mouse; D054407:Chemokine CCL4; D019402:Macrophage Inflammatory Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine