However, cell-surface Ctype lectin DC-SIGN, mainly expressed by DC, is believed to be one of the most important receptors for DENV. DC-SIGN is a member of the calcium-dependent C-type lectin family and recognizes high-mannose glycans present on different pathogens such as human immunodeficiency virus, hepatitis C virus, ebola virus and several bacteria, parasites and yeasts. Many of these pathogens have developed strategies to manipulate DC-SIGN interaction to escape from an immune response. Besides DC, macrophages play a key role in the immunopathogenesis of DENV infection. Recently, it was shown that the mannose receptor mediates DENV infection in macrophages by recognition of the Butenafine hydrochloride glycoproteins on the viral envelope. Monocyte-derived DC, isolated from human donor blood, may not represent all in vivo DC subsets but they express both MR and DC-SIGN which make MDDC susceptible for DENV. In most tissues, DC are in an immature state and they can capture the antigen because of their expression of attachment receptors, such as DC-SIGN. Following antigen capture in the periphery, DC maturate by upregulating their co-stimulatory molecules and migrate to lymphoid organs. Activated DC are stimulators of naive T-cells and they initiate production of cytokines and chemokines. Inhibition of the initial interaction between DENV and DC could prevent an immune response and subsequently prevent cytokine release responsible for vascular leakage. DC-SIGN could be a target for antiviral therapy by interrupting the viral entry process. Dendritic cells and macrophages are the cellular targets for DENV. The four DENV serotypes used in our experiments were grown in the insect cell line C6/36 to mimic the first encounter of the DC with DENV. Thereby, infection of human primary MDDC 
with mosquito-derived DENV represents a good in vitro model to investigate the entry Folinic acid calcium salt pentahydrate mechanism of DENV and the activity of specific antiviral compounds. DENV-infected DC and macrophages play a key role in the immunopathogenesis of dengue hemorrhagic fever by the production of proinflammatory cytokines, chemokines, metalloproteinases and the induction of cell maturation. In most tissues, DC are in an immature state, unable to stimulate T-cells. They lack the expression of CD40 and CD86, the prerequisite for accessory signals for T-cell activation. However, immature DC are equipped with attachment receptors, such as DC-SIGN, to capture diverse pathogens. We generated immature DCSIGN expressing MDDC out of primary monocytes. Addition of IL-4 and GM-CSF to monocytes induces cell differentiation, DCSIGN expression and enhances DENV susceptibility, consistent with other studies. DC-SIGN is nowadays hypothesized to be the main receptor for DENV, because it renders unsusceptible cells susceptible for DENV infection and DC-SIGN is highly expressed in immature DC. Another possible receptor for DENV is MR, expressed in immature DC and macrophages. We confirm that DC-SIGN is an important receptor for DENV infection, because DC-SIGN-specific antibodies profoundly inhibit DENV infection of MDDC. Furthermore, the combination of anti-DC-SIGN and anti-MR antibodies was even more effective in inhibiting DENV infection. Yet complete inhibition of DENV infection was not achieved, indicating that other entry pathways are potentially involved. In the case of HIV, DC-SIGN is found to be an important attachment receptor on DC to capture HIV and transmit the virus to resting T-cells. DCSIGN-independent pathways for the transmission of HIV must exist, since anti-DC-SIGN mAbs and DC-SIGN small interfering RNA did not completely inhibit the transmission of HIV from DC to T-cells.