CCR2 regulates development of Theiler's murine encephalomyelitis virus-induced demyelinating disease.
Theiler's murine encephalomyelitis virus (TMEV)-induced demyelinating disease, a murine model for multiple sclerosis, involves recruitment of T cells and macrophages to the CNS after infection. We hypothesized that CCR2, the only known receptor for CCL2, would be required for TMEV-induced demyelinating disease development because of its role in macrophage recruitment. TMEV-infected SJL CCR2 knockout (KO) mice showed decreased long-term clinical disease severity and less demyelination compared with controls. Flow cytometric data indicated that macrophages (CD45(high) CD11b(+) ) in the CNS of TMEV-infected CCR2 KO mice were decreased compared with control mice throughout disease. CD4(+) and CD8(+) T cell percentages in the CNS of TMEV-infected control and CCR2 KO mice were similar over the course of disease. There were no apparent differences between CCR2 KO and control peripheral immune responses. The frequency of interferon-gamma-producing T cells in response to proteolipid protein 139-151 in the CNS was also similar during the autoimmunity stage of TMEV-induced demyelinating disease. These data suggest that CCR2 is important for development of clinical disease by regulating macrophage accumulation after TMEV infection.
Bennett
Jami L
JL
Department of Pathology, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA.
Elhofy
Adam
A
Charo
Israel
I
Miller
Stephen D
SD
Dal Canto
Mauro C
MC
Karpus
William J
WJ
D000818:Animals; D001921:Brain / Q000473:pathology / Q000821:virology; D018188:Cardiovirus Infections / Q000150:complications*; D003711:Demyelinating Diseases / Q000209:etiology* / Q000473:pathology / Q000821:virology; D007371:Interferon-gamma / Q000096:biosynthesis; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054390:Receptors, CCR2; D019707:Receptors, Chemokine / Q000502:physiology*; D017945:Theilovirus / Q000276:immunology; D019562:Viral Load
C515335:Ccr2 protein, mouse; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D007371:Interferon-gamma