Molecular mechanisms controlling dendritic cell functions in HIV-1 and Ebolavirus infection

Mucosal immune cells play an important role in the defense against invading pathogens, and help to constitute a strong initial barrier. Dendritic cells (DCs) are seeded in the mucosa to function as sentinels of incoming harmful microbes and to initiate adaptive immunity. In this thesis we have aimed to elucidate what the role of DCs and Langerhans cells (LCs) is at the earliest events during infection by HIV-1 and Ebolavirus (EBOV). We focused on the C-type lectin receptors (CLR) langerin and DC-SIGN and the molecular mechanisms of evasive strategies employed by these viruses. We have demonstrated that HIV-1 exploits host factors in DCs to evade immunity during replication, whereby we were able to identify DDX3 as a novel sensor for HIV-1 in DCs. Furthermore we identified a novel trait of ‘successfully’ transmitted HIV-1 viruses in infecting mucosal LCs, which underscores the potential of these cells to restrict HIV-1 during sexual transmission. And lastly, we presented pioneering work that investigates the role of LCs during EBOV invasion, indicating that these cells might have an important barrier function against EBOV. Collectively, our research described in this thesis and the identification of molecular mechanisms provide exciting new insights that may have implications for the development of novel therapeutic approaches