Dendritic cell apoptosis and the pathogenesis of dengue

Abstract

Dengue viruses and other members of the Flaviviridae family are emerging human pathogens. Dengue is transmitted to humans by Aedes aegypti female mosquitoes. Following infection through the bite, cells of the hematopoietic lineage, like dendritic cells, are the first targets of dengue virus infection. Dendritic cells (DCs) are key antigen presenting cells, sensing pathogens, processing and presenting the antigens to T lymphocytes, and triggering an adaptive immune response. Infection of DCs by dengue virus may induce apoptosis, impairing their ability to present antigens to T cells, and thereby contributing to dengue pathogenesis. This review focuses on general mechanisms by which dengue virus triggers apoptosis, and possible influence of DC-apoptosis on dengue disease severity.

Figure 1

Incidence of dengue fever (blue bars) and dengue hemorrhagic fever (red line) in Brazil since its re-introduction in 1986.

Figure 2

Possible mechanisms by which dengue virus may induce apoptosis of Dendritic cells (DCs). Dengue virus (DENV) can directly induce DC-apoptosis through replication inside infected cells. Apoptosis may also be induced in infected and uninfected-DC via exosomes, cytokines and viral proteins secreted from infected DCs. It has been demonstrated that TNF-α protects DCs from apoptosis induced by DENV, possibly inducing DC maturation. Also, structural and non-structural viral proteins may either induce apoptosis or protect DC from apoptosis. Finally, induction of apoptosis by DENV in infected and uninfected DC presumably contributes to dengue pathogenesis by promoting high viremia, production of inflammatory cytokines, reduced antigen-presentation and low DENV-specific T-cell activation.