Abstract
Ebola virus (EBOV) causes severe systemic disease in humans and non-human primates characterized by high levels of viremia and virus titers in peripheral organs. The natural portals of virus entry are the mucosal surfaces and the skin where macrophages and dendritic cells (DCs) are primary EBOV targets. Due to the migratory properties of DCs, EBOV infection of these cells has been proposed as a necessary step for virus dissemination via draining lymph nodes and blood. Here we utilize chimeric mice with competent hematopoietic-driven immunity, to show that EBOV primarily infects CD11b+ DCs in non-lymphoid and lymphoid tissues, but spares the main cross-presenting CD103+ DC subset. Furthermore, depletion of CD8 and CD4 T cells resulted in loss of early control of virus replication, viremia and fatal Ebola virus disease (EVD). Thus, our findings point out at T cell function as a key determinant of EVD progress and outcome.
Highlights
Flt[3] but are morphologically and functionally distinct
Our results indicated that loss of IFN-I responsiveness in the hematopoietic compartment resulted in virus dissemination suggesting a putative correlation between infection of IFN-deficient cells and virus spread in our model
Previous research has shown that EBOV infects DCs and macrophages derived in vitro from hematopoietic progenitors which was consistent with early studies showing the presence of EBOV virions in dendritic-like cells in tissue sections[3,4,5,6]
Summary
Inflammatory DCs are derived from activated monocytes that infiltrate tissues during inflammation or infection[11]. Previous in vitro experiments of EBOV infection of monocyte-derived DCs do not reflect the variety of DC subsets in living organisms. It is not known whether EBOV is capable of infecting all DC subsets in vivo. EBOV productively infected resident macrophages and CD11b+ DCs in peripheral tissues and draining lymph nodes. Our results identified infected CD11b+ DCs as putative viral vessels and underscored a key role of T cells as controllers of EBOV infection at the initial points of virus entry
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