title: The role of interleukin-6 in the expression of PD-1 and PDL-1 on central nervous system cells following infection with Theiler's murine encephalomyelitis virus.
abstract: Infection with Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) of susceptible mice results in an immune-mediated demyelinating disease which is considered a relevant viral model of human multiple sclerosis. We previously demonstrated that the expression of positive costimulatory molecules (CD40, CD80, and CD86) is higher on the microglia of TMEV-resistant C57BL/6 (B6) mice than the microglia of TMEV-susceptible SJL/J (SJL) mice. In this study, we analyzed the expression levels of the negative costimulatory molecules PD-1 and PDL-1 in the CNS of TMEV-infected SJL mice and B6 mice. Our results indicated that TMEV infection induces the expression of both PD-1 and PDL-1 on microglia and macrophages in the CNS but not in the periphery. The expression of PD-1 only on CNS-infiltrating macrophages and not on resident microglia was considerably higher (>4-fold) in TMEV-infected SJL mice than TMEV-infected B6 mice. We further demonstrated that interleukn-6 (IL-6) is necessary to induce the maximal expression of PDL-1 but not PD-1 after TMEV infection using IL-6-deficient mice and IL-6-transgenic mice in conjunction with recombinant IL-6. In addition, cells from type I interferon (IFN) receptor knockout mice failed to upregulate PD-1 and PDL-1 expression after TMEV infection in vitro, indicating that type I IFN signaling is associated with the upregulation. However, other IFN signaling may also participate in the upregulation. Taken together, these results strongly suggest that the expression of PD-1 and PDL-1 in the CNS is primarily upregulated following TMEV infection via type I IFN signaling and the maximal expression of PDL-1 additionally requires IL-6 signaling.
authors: Department of Microbiology-Immunology, Northwestern University Medical School, Chicago, Illinois, USA.
authors: Young-Hee
authors: YH
authors: Jin
authors: Wanqiu
authors: W
authors: Hou
authors: Hyun Seok
authors: HS
authors: Kang
authors: Chang-Sung
authors: CS
authors: Koh
authors: Byung S
authors: BS
authors: Kim
mesh_terms: D000818:Animals; D060890:B7-H1 Antigen / Q000378:metabolism*; D018188:Cardiovirus Infections / Q000276:immunology / Q000821:virology*; D002490:Central Nervous System / Q000821:virology*; D005260:Female; D015850:Interleukin-6 / Q000276:immunology*; D008264:Macrophages / Q000821:virology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D017628:Microglia / Q000821:virology*; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism*; D017945:Theilovirus / Q000276:immunology*
chemical_list: D060890:B7-H1 Antigen; D015850:Interleukin-6; D061026:Programmed Cell Death 1 Receptor
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