Sensing dengue and chikungunya virus (co-) infections

Dengue and chikungunya are two of the most important diseases transmitted by mosquitos. Over the past decades their global burden has increased dramatically. Furthermore, due to the geographic overlap of both viruses as well as their common mosquito vectors, the incidence of dengue and chikungunya co-infections is also increasing. The clinical manifestations of the acute phase of dengue and chikungunya virus induced disease are very similar making their diagnosis a real challenge. In this thesis, we investigated the role of monocytes, a cell type within the immune system that protects and combats infectious diseases. Our work shows that monocytes can sense dengue and chikungunya viruses resulting in the production of inflammatory mediators that may contribute to disease burden. By analyzing blood samples from dengue virus infected children, we discovered a role for toll-like receptor (TLR2) as a sensor of DENV infection and identified a prognostic value of its expression in a subset of monocytes known as classical monocytes. We found that TLR2 on monocytes is also able to detect fully immature dengue particles. In addition, our studies described the effect of dengue and chikungunya virus co-infections in vitro in primary human primary cells. However, there are still knowledge gaps of these diseases that need to be further investigated in order to understand the role of monocytes in the immunopathology of these diseases. The use of high-dimensional molecular biology techniques will be crucial to address these gaps and help us to develop new therapies to combat dengue and chikungunya virus infections