Innate and B cell-dependent immune responses to dengue virus infection

Dengue is an important mosquito-borne disease caused by dengue virus, which primarily affects children in tropical and sub-tropical countries. The disease presentation varies from mostly asymptomatic to mild or severe disease. In this thesis, we evaluated the impact of dengue infection on innate and B cell-dependent immune responses by analyzing blood samples obtained from Cambodian children early during infection. We demonstrate that dengue virus is sensed by monocytes through receptors TLR2 and CD14 and that monocytes can be infected by dengue virus. This induces an inflammatory response against viral infection, which can be beneficial or detrimental to the host. A potential outcome of this inflammatory response is the extracellular release of the soluble forms of TLR2 and CD14 in the blood. We found that detection of soluble CD14 in serum may help in identifying patients at risk of developing severe dengue. Next, we showed that increased production of antiviral type I interferons by plasmacytoid dendritic cells correlates with mild dengue and may influence antibody production by B cells. We also described the effect of dengue infection on B cells and its consequence on their antibody-independent functions. B cells were found permissive to dengue virus infection and infection impairs their activation and cytokine production. Overall, our data provides a better understanding of immune responses mediated by various immune cells during dengue infection and their associations with different clinical outcomes of dengue. However, the interactions between these immune cells in the context of dengue infection are not fully elucidated and are under investigation