Toso regulates differentiation and activation of inflammatory dendritic cells during persistence-prone virus infection

Cell Death Differ. 2015 Jan;22(1):164-73. doi: 10.1038/cdd.2014.138. Epub 2014 Sep 26.

Abstract

During virus infection and autoimmune disease, inflammatory dendritic cells (iDCs) differentiate from blood monocytes and infiltrate infected tissue. Following acute infection with hepatotropic viruses, iDCs are essential for re-stimulating virus-specific CD8(+) T cells and therefore contribute to virus control. Here we used the lymphocytic choriomeningitis virus (LCMV) model system to identify novel signals, which influence the recruitment and activation of iDCs in the liver. We observed that intrinsic expression of Toso (Faim3, FcμR) influenced the differentiation and activation of iDCs in vivo and DCs in vitro. Lack of iDCs in Toso-deficient (Toso(-/-)) mice reduced CD8(+) T-cell function in the liver and resulted in virus persistence. Furthermore, Toso(-/-) DCs failed to induce autoimmune diabetes in the rat insulin promoter-glycoprotein (RIP-GP) autoimmune diabetes model. In conclusion, we found that Toso has an essential role in the differentiation and maturation of iDCs, a process that is required for the control of persistence-prone virus infection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology
  • Carrier Proteins / genetics
  • Carrier Proteins / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Dendritic Cells / immunology*
  • Dendritic Cells / pathology
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / immunology
  • Diabetes Mellitus, Experimental / pathology
  • Immunity, Cellular
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / pathology
  • Liver / immunology
  • Liver / pathology
  • Lymphocytic Choriomeningitis / genetics
  • Lymphocytic Choriomeningitis / immunology*
  • Lymphocytic Choriomeningitis / pathology
  • Lymphocytic choriomeningitis virus / immunology*
  • Membrane Proteins / genetics
  • Membrane Proteins / immunology*
  • Mice
  • Mice, Knockout
  • Rats

Substances

  • Carrier Proteins
  • Fcmr protein, mouse
  • Membrane Proteins