Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells

Abstract

Manipulation of immune cell functions, independently of direct infection of these cells, emerges as a key process in viral pathophysiology. Chronic infection by Human T-cell Leukemia Virus type 1 (HTLV-1) is associated with immune dysfunctions, including misdirected responses of dendritic cells (DCs). Here, we interrogate the ability of HTLV-1-infected T cells to indirectly manipulate human DC functions. We show that upon coculture with chronically infected T cells, monocyte-derived DCs (MDDCs) fail to fully mature. We further show that exposure to HTLV-1-infected T cells induces a unique transcriptional signature in MDDCs, which differs from a typical maturation program, and which is correlated with a dampened ability of HTLV-1-exposed MDDCs to subsequently respond to restimulation. Induction of this tolerogenic behavior is not strictly dependent on capture of HTLV-1 viral particles by MDDCs, nor on cell-cell contacts between HTLV-1-infected T cells and MDDCs, but is instead the result of a molecular dialogue between HTLV-1-infected T cells and MDDCs upon coculture, illustrating how HTLV-1 might indirectly induce a local tolerogenic immune microenvironment suitable for its own persistence.