Abstract
Theiler's murine encephalomyelitis virus induces a demyelinating disease (TMEV-IDD) of the central nervous system (CNS) in susceptible mouse strains with accompanying histopathology characterized by mononuclear cell infiltrates. In susceptible strains of mice such as SJL, virus establishes a persistent infection in macrophages, induces a CNS infiltration by macrophages, T cells, and B cells, which results in chronic-progressive paralysis. In the present report the authors have investigated the functional role of CCL2 (monocyte chemotactic protein-1) in the induction and progression of demyelinating disease. Treatment of infected mice at day 0, 14, or 28 with anti-CCL2 resulted in a significant decrease in the clinical disease progression. Further analysis of anti-CCL2–treated mice revealed decreased CNS inflammation and mononuclear cell infiltration with an accompanying change in inflammatory cytokine responses. There was an overall decrease in the absolute numbers of CNS-infiltrating CD4+ T cells, macrophages, and B cells. Finally, anti-CCL2 treatment resulted in decreased viral load in the CNS. These data directly demonstrate a role for CCL2 in the pathogenesis of TMEV-IDD.
| Abbreviations | ||
| BHK-21, | = | baby hamster kidney cell line 21; |
| BSA, | = | bovine serum albumin; |
| CCL2, | = | monocyte chemotactic protein-1; |
| CCL3, | = | macrophage inflammatory protein-1α; |
| CCL4, | = | macrophage inflammatory protein-1β; |
| CCL5, | = | RANTES; |
| CNS, | = | central nervous system; |
| CXCL1, | = | macrophage inflammatory protein-2; |
| CXCL10, | = | gamma interferon inducible protein-10; |
| H&E, | = | hematoxylin and eosin; |
| NRS, | = | normal rabbit serum; |
| TMEV, | = | Theiler's murine encephalomyelitis virus; |
| TMEV-IDD, | = | Theiler's murine encephalomyelitis virus–induced demyelinating disease. |
| Abbreviations | ||
| BHK-21, | = | baby hamster kidney cell line 21; |
| BSA, | = | bovine serum albumin; |
| CCL2, | = | monocyte chemotactic protein-1; |
| CCL3, | = | macrophage inflammatory protein-1α; |
| CCL4, | = | macrophage inflammatory protein-1β; |
| CCL5, | = | RANTES; |
| CNS, | = | central nervous system; |
| CXCL1, | = | macrophage inflammatory protein-2; |
| CXCL10, | = | gamma interferon inducible protein-10; |
| H&E, | = | hematoxylin and eosin; |
| NRS, | = | normal rabbit serum; |
| TMEV, | = | Theiler's murine encephalomyelitis virus; |
| TMEV-IDD, | = | Theiler's murine encephalomyelitis virus–induced demyelinating disease. |
This work was supported by The National Multiple Sclerosis Society grant RG 3056-A-2 and NIH grant P01 NS023349 (WJK).