title: IL-1R1 is required for dendritic cell-mediated T cell reactivation within the CNS during West Nile virus encephalitis.
abstract: Infections of the central nervous system (CNS) with cytopathic viruses require efficient T cell responses to promote viral clearance, limit immunopathology, and enhance survival. We found that IL-1R1 is critical for effector T cell reactivation and limits inflammation within the CNS during murine West Nile virus (WNV) encephalitis. WNV-infected IL-1R1(-/-) mice display intact adaptive immunity in the periphery but succumb to WNV infection caused by loss of virologic control in the CNS with depressed local Th1 cytokine responses, despite parenchymal entry of virus-specific CD8(+) T cells. Ex vivo analysis of CD4(+) T cells from WNV-infected CNS of IL-1R1(-/-) mice revealed impaired effector responses, whereas CD8(+) T cells revealed no cell intrinsic defects in response to WNV antigen. WNV-infected, IL-1R1(-/-) mice also exhibited decreased activation of CNS CD11c(+)CD11b(-)CD103(+) and CD11c(+)CD11b(-)CD8α(+)Dec-205(+) cells with reduced up-regulation of the co-stimulatory molecules CD80, CD86, and CD68. Adoptive transfer of wild-type CD11c-EYFP(+) cells from WNV-infected CNS into WNV-infected IL-1R1(-/-) mice trafficked into the CNS restored T cell functions and improved survival from otherwise lethal infection. These data indicate that IL-1R1 signaling promotes virologic control during WNV infection specifically within the CNS via modulation of CD11c(+) cell-mediated T cell reactivation at this site.
authors: Department of Internal Medicine, Washington University School of Medicine in St. Louis, St. Louis, MO 63110, USA.
authors: Douglas M
authors: DM
authors: Durrant
authors: Michelle L
authors: ML
authors: Robinette
authors: Robyn S
authors: RS
authors: Klein
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D001921:Brain / Q000276:immunology*; D039521:CD11c Antigen / Q000032:analysis; D003713:Dendritic Cells / Q000276:immunology*; D018792:Encephalitis, Viral / Q000276:immunology*; D006801:Humans; D007375:Interleukin-1 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D053573:Receptors, Interleukin-1 Type I / Q000502:physiology*; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D014901:West Nile Fever / Q000276:immunology*
chemical_list: D039521:CD11c Antigen; D007375:Interleukin-1; D053573:Receptors, Interleukin-1 Type I