The innate immune defense plays an important role in the recognition and control of viral infections. A crucial component of this system are the plasmacytoid dendritic cells (PDC), which have recently been identified as major producers of type I interferons in the blood. Our results show that not HIV itself, but HIV-infected cells are important for the induction of interferon production, maturation, and migration of PDC. This response seems to be mediated by the recognition of virus-infected cells via specific surface receptors, endocytotic processes and signal transduction via Toll-like receptors. Based on findings obtained by chip analysis during the past funding period, these molecular mechanisms will be evaluated in three respects: (i) which viral determinants are responsible for interferon induction and HIV pathogenicity, (ii) how Toll-like receptors and intracellular signal transduction are involved in PDC maturation and migration, and (iii) which cellular molecule expressed on virus-infected cells initiates the signaling cascade. The results of this project will elucidate the role of PDC and mature dendritic cells for the control of HIV infection and HIV pathogenesis. In addition, targets will be identified which will offer new therapeutic approaches for modifying innate immune responses.
