[Plasmacytoid dendritic cell responses to adult and neonatal TLR7 & 9 ligands].

Abstract

The plasmacytoid dendritic cells (pDCs) belong to the innate immune system and are responsible for the production of type interferons (IFN-I). These are crucial for the antiviral and antitumoral responses of the organism. Newborns are unable to produce IFN-I in response to viral infections, due to the absence of nuclear translocation of the transcription factor IRF7 in their pDCs. We have shown that this defect is due to the deficient phosphorylation of this factor, and that the PI3K-Akt-mTOR-pathway, on the other hand is functional. We have also shown, this time in adult pDCs, that the PI3K-Akt-mTOR-pathway, known to be absolutely necessary for the production of IFN-I in response to TLR9-ligands and RNA viruses, is surprisingly not required for this production in response to synthetic TLR7 ligands. These ligands are used in the clinic as vaccine adjuvants, antiviral and antitumoral agents. The inhibitors of PI3K and + mTOR are in use as immunosuppressors and adjuvants for chemotherapy, making these interactions clinically highly relevant.