title: Ligand up-regulation does not correlate with a role for CCR1 in pathogenesis in a mouse model of non-lymphocyte-mediated neurological disease.
abstract: CCR1 ligands, including CCL3, CCL5, and CCL7, are up-regulated in a number of neurological disorders in humans and animal models. CCR1 is expressed by multiple cell types in the central nervous system (CNS), suggesting that receptor signaling by neuronal cell types may influence pathogenesis. In the current study, the authors used a mouse model of retrovirus infection to study the contribution of CCR1 to neuropathogenesis in the absence of lymphocyte recruitment to the CNS. In this model, infection of neonatal mice with the neurovirulent retrovirus Fr98 results in increased expression of proinflammatory chemokines in the CNS, activation of glial cells, and development of severe neurological disease. Surprisingly, no difference in neuropathogenesis was observed between CCR1-sufficient and CCR1-deficient mice following infection with the neuropathogenic virus Fr98. CCR1 was also not necessary for control of virus replication in the brain or virus-induced activation of astroglia. Additionally, CCR1 deficiency did not affect the up-regulation of its ligands, CCL3, CCL5, or CCL7. Thus, CCR1 did not appear to have a notable role in Fr98-induced pathogenesis, despite the correlation between ligand expression and disease development. This suggests that in the absence of inflammation, CCR1 may have a very limited role in neuropathogenesis.
authors.affiliation: Department of Pathobiological Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, Louisiana 70803, USA.
authors.forename: Meryll E
authors.initials: ME
authors.lastname: Corbin
authors.forename: Susan
authors.initials: S
authors.lastname: Pourciau
authors.forename: Timothy W
authors.initials: TW
authors.lastname: Morgan
authors.forename: Marc
authors.initials: M
authors.lastname: Boudreaux
authors.forename: Karin E
authors.initials: KE
authors.lastname: Peterson
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC / Q000096:biosynthesis / Q000235:genetics; D005260:Female; D008214:Lymphocytes / Q000276:immunology / Q000473:pathology; D019402:Macrophage Inflammatory Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018945:Monocyte Chemoattractant Proteins / Q000096:biosynthesis / Q000235:genetics; D009422:Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D054389:Receptors, CCR1; D019707:Receptors, Chemokine / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D012190:Retroviridae / Q000502:physiology; D012192:Retroviridae Infections / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014779:Virus Replication
chemical_list: C496534:Ccl3 protein, mouse; C503460:Ccl5 protein, mouse; C515451:Ccl7 protein, mouse; C515301:Ccr1 protein, mouse; D054405:Chemokine CCL3; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D019742:Chemokines, CC; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D054389:Receptors, CCR1; D019707:Receptors, Chemokine