Abstract
Langerhans cells (LCs) are tissue resident antigen-presenting cells (APCs), and are part of our first line of defense. LCs are found not only in mucous membranes and others lymphoid tissues, but also in the skin, one of the main pathways of entry for pathogens. Involved in many antiviral responses, LCs are able to scan the environment in search of pathogens using their cytoplasmic projections. In addition to pathogen detection, LCs also play a poorly understood role following the response to vaccines. During my thesis, I explored the role(s) LCs play in adenovirus-based vaccination. Given the widespread use of certain adenovirus types in vaccines, it is critical to elucidate the immune mechanisms involved and the key cellular actors.To this end, I combined in vitro and ex vivo approaches to mimic a physiologically context. Initially we developed a robust cell model (from CD34+ cells from umbilical cord blood) to characterized the uptake of adenovirus type C5, D26 and B35 vectors by in vitro differenciated LCs and their response (inflammatory and antiviral cytokine profile). To validate our findings in a more complex and physiologically accurate system, we also utilized human skin samples. Adenoviral vectors (HAdV-C5, -D26, and -B35) were injected into skin samples from healthy donors to observe LC uptake and their localization within the tissue during the vaccination process.My results suggested that the injection of vectors derived from the different adenoviral types induced the recruitment of LCs to the injection site, suggesting an initiating role in the response to adenovirus-based vaccines. Indeed, both CD34-LCs and skin-resident LCs were able to take up adenoviral vectors. While the different adenoviral types elicited distinct phenotypic changes in LCs, the cells consistently adopted antiviral and pro-inflammatory cytokine profiles. Additionally, LCs underwent morphological changes that may correlate with their migration, as observed in the human skin model.Taken together, these elements constitute a first step towards understanding the role of LCs and characterizing the mechanism by which adenoviral -based vaccines induce protection. This knowledge provides a foundation to further improve vaccine strategies and exploiting specific molecules to amplify LC-mediated immune responses.