Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells - Archive ouverte HAL
Article Dans Une Revue PLoS Pathogens Année : 2024

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

Auriane Carcone
  • Fonction : Auteur
Franck Mortreux
  • Fonction : Auteur
Sandrine Alais
  • Fonction : Auteur
Chloé Journo
  • Fonction : Auteur
Hélène Dutartre

Résumé

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 transformed HTLV-1infected T cells to manipulate human DC functions. We show that exposure to transformed HTLV-1-infected T cells induces a biased and peculiar transcriptional signature in monocyte-derived DCs, associated with an inefficient maturation and a poor responsiveness to subsequent stimulation by a TLR4 agonist. This poor responsiveness is also associated with a unique transcriptional landscape characterized by a set of genes whose expression is either conferred, impaired or abolished by HTLV-1 pre-exposure. Induction of this functional impairment requires several hours of coculture with transformed HTLV-1-infected cells, and associated mechanisms driven by viral capture, cell-cell contacts, and soluble mediators. Altogether, this cross-talk between infected T cells and DCs illustrate how HTLV-1 might coopt communications between cells to induce a unique local tolerogenic immune microenvironment suitable for its own persistence.

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Virologie
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hal-04743334 , version 1 (18-10-2024)

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Auriane Carcone, Franck Mortreux, Sandrine Alais, Cyrille Mathieu, Chloé Journo, et al.. Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells. PLoS Pathogens, 2024, 20 (9), pp.e1012555. ⟨10.1371/journal.ppat.1012555⟩. ⟨hal-04743334⟩
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