| First Author | Jin YH | Year | 2013 |
| Journal | J Virol | Volume | 87 |
| Issue | 21 | Pages | 11538-51 |
| PubMed ID | 23966393 | Mgi Jnum | J:315251 |
| Mgi Id | MGI:6829908 | Doi | 10.1128/JVI.01967-13 |
| Citation | Jin YH, et al. (2013) 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. J Virol 87(21):11538-51 |
| abstractText | 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. |
