The role of conventional dendritic cell subsets in T-cell activation in Ebola virus infection

Abstract

Severe Ebola virus disease (EVD) is characterized by excess, dysregulated T cell activation and high levels of inflammation. In conflict with these clinical observations, in vitro studies described that Ebola virus (EBOV) infection of monocyte-derived dendritic cells (moDCs), results in suppression of T cell activation due to inhibition of DC activation. However, it is unknown how other DC subsets distinct from moDCs respond to EBOV infection. Therefore, we assessed the response of FMS-like tyrosine kinase 3 (Flt3)-dependent, conventional mouse DCs (cDCs) to EBOV infection, and studied their CD8 T-cell activation capacity in a DC-T cell co-culture system utilizing a recombinant EBOV expressing the model antigen ovalbumin. Our data indicate that EBOV infection of mouse cDCs, results in activation rather than inhibition, promotes antigen cross-presentation and thus, leads to high levels of CD8 T cell activation. With that, we propose a mechanistic explanation for the excess T cell activation observed in severe human EVD.