Type I interferon signals control Theiler's virus infection site, cellular infiltration and T cell stimulation in the CNS.
Theiler's murine encephalomyelitis virus (TMEV) establishes a persistent infection in the central nervous system (CNS). To examine the role of type I interferon (IFN-I)-mediated signals in TMEV infection, mice lacking a subunit of the type I IFN receptor (IFN-IR KO mice) were utilized. In contrast to wild type mice, IFN-IR KO mice developed rapid fatal encephalitis accompanied with greater viral load and infiltration of immune cells to the CNS. The proportion of virus-specific CD4(+) and CD8(+) T cell responses in the CNS was significantly lower in IFN-IR KO mice during the early stage of infection. Levels of IFN-γ and IL-17 produced by isolated primed CD4(+) T cells in response to DCs from TMEV-infected IFN-IR KO mice were also lower than those stimulated by DCs from TMEV-infected wild type control mice. The less efficient stimulation of virus-specific T cells by virus-infected antigen-presenting cells is attributable in part to the low level expression of activation markers on TMEV-infected cells from IFN-IR KO mice. However, due to high levels of cellular infiltration and viral loads in the CNS, the overall numbers of virus-specific T cells are higher in IFN-IR KO mice during the later stage of viral infection. These results suggest that IFN-I-mediated signals play important roles in controlling cellular infiltration to the CNS and shaping local T cell immune responses.
Department of Microbiology-Immunology, Northwestern University Medical School, 303 E. Chicago, IL 60611, USA.
Young-Hee
YH
Jin
Wanqiu
W
Hou
Seung Jae
SJ
Kim
Alyson C
AC
Fuller
Bongsu
B
Kang
Gwen
G
Goings
Stephen D
SD
Miller
Byung S
BS
Kim
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D002490:Central Nervous System / Q000276:immunology* / Q000821:virology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004769:Enterovirus Infections / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D007370:Interferon Type I / Q000172:deficiency; D020381:Interleukin-17 / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology*; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency; D015398:Signal Transduction / Q000276:immunology* / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology* / Q000821:virology; D017945:Theilovirus / Q000472:pathogenicity
D016207:Cytokines; C508032:Ifnar1 protein, mouse; D007370:Interferon Type I; D020381:Interleukin-17; D053633:Receptor, Interferon alpha-beta