In vivo functions of nuclear envelope rupture and antiviral specialization in dendritic cells

ended

Dendritic cells (DCs) function at the interface between innate and adaptive immunity and have a crucial role in the induction of immune responses. The goal of this project is to uncover the in vivo functions of two novel molecular mechanisms that were recently identified in vitro in DCs. DCs are rapidly activated when DNA is exposed to the cytosol, which can occur in viral infections. Recent work has revealed that DNA is also transiently accessible to the cytosol in migrating DCs due to rupture of the nuclear envelope, and is detected by the cytosolic DNA sensor cGAS. In the first aim of this project we will investigate the immune consequences of nuclear envelope rupture in DCs in vivo. The second aim of this project is to investigate antiviral specialization of DC subsets. Viral infection of DCs impairs their immune functions. Unpublished data has revealed that in humans, the CD141+ DC subset is constitutively resistant to a broad range of enveloped viruses. Resistance was associated with the expression of the GTPase, RAB15. We will investigate the function of RAB15 in DC biology in vivo to study the division of antiviral labor among DC subsets.