Differential virus replication, cytokine production, and antigen-presenting function by microglia from susceptible and resistant mice infected with Theiler's virus.
Infection with Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) causes an immune system-mediated demyelinating disease similar to human multiple sclerosis in susceptible but not resistant strains of mice. To understand the underlying mechanisms of differential susceptibility, we analyzed viral replication, cytokine production, and costimulatory molecule expression levels in microglia and macrophages in the CNS of virus-infected resistant C57BL/6 (B6) and susceptible SJL/J (SJL) mice. Our results indicated that message levels of TMEV, tumor necrosis factor alpha, beta interferon, and interleukin-6 were consistently higher in microglia from virus-infected SJL mice than in those from B6 mice. However, the levels of costimulatory molecule expression, as well as the ability to stimulate allogeneic T cells, were significantly lower in TMEV-infected SJL mice than in B6 mice. In addition, microglia from uninfected naïve mice displayed differential viral replication, T-cell stimulation, and cytokine production, similar to those of microglia from infected mice. These results strongly suggest that different levels of intrinsic susceptibility to TMEV infection, cytokine production, and T-cell activation ability by microglia contribute to the levels of viral persistence and antiviral T-cell responses in the CNS, which are critical for the differential susceptibility to TMEV-induced demyelinating disease between SJL and B6 mice.
Jin
Young-Hee
YH
Department of Microbiology and Immunology, Northwestern University Feinberg Medical School, 303 E. Chicago Avenue, Chicago, IL 60611, USA.
Mohindru
Mani
M
Kang
Min H
MH
Fuller
Alyson C
AC
Kang
Bongsu
B
Gallo
Daniel
D
Kim
Byung S
BS
D000818:Animals; D017951:Antigen Presentation; D002460:Cell Line; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D010455:Peptides / Q000737:chemistry; D013601:T-Lymphocytes / Q000378:metabolism / Q000821:virology; D017945:Theilovirus / Q000378:metabolism*; D013997:Time Factors; D014779:Virus Replication
D016207:Cytokines; D010455:Peptides
Immunology. 1993 Nov;80(3):502-6
7904593
J Virol. 1998 Jul;72(7):6169-74
9621084
Nat Med. 2005 Mar;11(3):328-34
15735653
Glia. 2006 Jun;53(8):858-67
16586493
Ann Neurol. 1983 Apr;13(4):426-33
6340596
Virology. 2000 Dec 20;278(2):346-60
11118358
J Immunol. 1995 May 1;154(9):4309-21
7722289
J Exp Med. 1937 Apr 30;65(5):705-19
19870629
J Neurosci Res. 2005 Aug 1;81(3):374-89
15959904
J Immunol. 1994 Nov 15;153(10):4508-19
7525707
J Immunol. 1995 Nov 1;155(9):4497-503
7594613
PLoS Pathog. 2007 Aug 24;3(8):e124
17722981
Virus Res. 2005 Aug;111(2):214-23
15893838
Neurology. 1986 Jul;36(7):964-70
3487048
J Virol. 2001 Sep;75(17):7811-7
11483724
J Virol. 2000 Sep;74(18):8349-57
10954534
Science. 1976 Apr 2;192(4234):62-4
176726
Eur J Immunol. 2004 Oct;34(10):2730-9
15368289
J Clin Invest. 1999 Sep;104(5):599-610
10487774
Neurology. 1984 Aug;34(8):1117-9
6087205
J Virol. 2001 Oct;75(20):9780-9
11559811
Int Immunol. 1996 Jul;8(7):1001-8
8757945
J Immunol. 1998 Jun 1;160(11):5320-30
9605131
Immunol Today. 1994 Jul;15(7):321-31
7522010
J Neuroimmunol. 2001 Jul 2;117(1-2):166-70
11431017
J Neuroimmunol. 1996 May;66(1-2):11-22
8964904
Annu Rev Immunol. 1996;14:233-58
8717514
J Immunol. 1994 Jan 15;152(2):919-29
7506740
Int Immunol. 1990;2(9):909-13
2279004
J Immunol. 2004 Sep 15;173(6):3916-24
15356140
Eur J Immunol. 2006 Aug;36(8):2106-15
16761311
Annu Rev Immunol. 1998;16:111-35
9597126
Immunol Res. 2005;31(1):1-12
15591618
J Gen Virol. 1999 Jul;80 ( Pt 7):1701-5
10423138
J Immunol. 1992 Oct 1;149(7):2473-81
1382105
J Neuroimmunol. 1997 Jun;76(1-2):213-23
9184653
Cell Mol Biol (Noisy-le-grand). 2001 Jun;47(4):609-17
11502069
Virus Res. 2005 Mar;108(1-2):57-61
15681055
J Neurosci Res. 2005 Nov 15;82(4):507-14
16237722
J Neurol Sci. 1976 Nov;30(1):201-7
978224
J Immunol. 1999 Jun 1;162(11):6543-51
10352270
J Virol. 1987 Mar;61(3):898-903
3492612
Virology. 2006 Sep 30;353(2):422-32
16824573
J Virol. 1995 Nov;69(11):7315-8
7474161
Virology. 1990 May;176(1):244-54
2158691
Nat Med. 1997 Oct;3(10):1133-6
9334726
Science. 1988 Jan 15;239(4837):290-2
3276004
J Virol. 2003 Jun;77(11):6322-31
12743289
J Exp Med. 1991 May 1;173(5):1235-46
1827142
J Exp Med. 1996 Nov 1;184(5):1737-45
8920862
J Immunol. 1996 May 15;156(10):4050-8
8621948
J Neuroimmunol. 1982 Jun;2(3-4):223-34
6282927
J Virol. 2002 Jul;76(13):6577-85
12050370
Brain Pathol. 2000 Jan;10(1):1-15
10668891
J Neurol. 2003 Dec;250 Suppl 4:IV3-8
14712395
J Immunol. 1994 Oct 15;153(8):3811-21
7930598
Expert Opin Pharmacother. 2005 Dec;6(16):2877-86
16318438