Microvesicles from T cells overexpress miR-146b-5p in HIV-1 infection and repress endothelial activation

• Published in: Journal of extracellular vesicles 2018-01, Vol.7, p.71-72
• Main Authors: Balducci, Estelle, Leroyer, Aurelie S, Lacroix, Romaric, Robert, Stéphane, Todorova, Dilyana, Simoncini, Stéphanie, Lyonnet, Luc, Chareyre, Corinne, Zaegel-Faucher, Olivia, Micallef, Joelle, Poizot-Martin, Isabelle, Roll, Patrice, Dignat-George, Françoise
• Format: Article
• Language: English
• Subjects: CD4 antigen; Cell activation; Cell interactions; Endothelial cells; Endothelium; HIV; Homeostasis; Human immunodeficiency virus; Infections; Infectious diseases; Inflammation; Intercellular adhesion molecule 1; IRAK protein; Lymphocytes; Lymphocytes T; miRNA; NF-κB protein; Paracrine signalling; Polymerase chain reaction; TRAF6 protein; Umbilical vein; Vascular cell adhesion molecule 1
• ISSN: 2001-3078

Background: Human immunodeficiency virus type 1 (HIV-1) promotes a generalized activation of host responses that involves not only CD4 T cells, but also cells of the microenvironment, which are not directly infected, such as endothelial cells. The mechanisms triggering HIV-1- associated vascular alterations remain poorly understood. Microvesicles (MVs), implicated in cell-to-cell communication, have been recently described as carriers of microRNAs (miRNAs). We hypothesized that HIV-1 infection induce cellular miRNA expression in CD4 T cells which may be vectorized by MVs and transferred in a paracrine manner to endothelial cells to regulate vascular homeostasis. Methods: Using a miRNome quantitative RT-PCR analysis, we showed that HIV-1 infection leads to a dysregulation of several miRNAs and identified miR-146b-5p as upregulated in both CD4 T cells, CD4 T cells derived-MVs and circulating MV obtained from antiretroviral therapynaive HIV-1-infected patients, compared to age- and sex-matched healthy subjects. We further used a CEM T cell line transfected with miR-146b-5p mimic to study the effects of MVs from CEM overexpressing miR-146b-5p mimic (miR-146b-MVs) on the endothelium. Results: Here, we show that MVs from T cell line overexpressing miR- 146b-5p mimics (miR-146b-MVs): (1) protect their miRNA cargo from RNase A degradation, (2) transfer miR-146b-5p mimic into human umbilical vein endothelial cell and (3) reduce endothelial inflammatory responses in vitro and in vivo in lungs from mice injected with miR- 146b-MVs. This paracrine control of endothelial inflammatory responses mediated by MVs involved decreased expression of nuclear factor-κB (NF-κB) responsive molecules, ICAM-1 and VCAM-1, through down-regulation of IRAK1 and TRAF6. Summary/Conclusion: These data advance our understanding on chronic inflammatory responses affecting endothelial homeostasis, in infectious and non-infectious diseases and pave the way for potential new anti-inflammatory strategies.