 |
 |
GEO help: Mouse over screen elements for information. |
|
| Status |
Public on Sep 05, 2024 |
| Title |
Peculiar transcriptional reprogramming with functional impairment of dendritic cells upon exposure to transformed HTLV-1-infected cells |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
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.
|
| |
|
| Overall design |
To understand how HTLV-1 infected transformed cell lines could modulate innate cell functions, we used dendritic cells generated from monocytes isolated from human blood using culture with GM-CSF and IL-4 (100ng/ml each) for 5 days. Then monocyte-derived dendritic cells (MDDCs) were co-cultured with HTLV-1 infected cell lines (C91PL, or C8166) or control non-infected T cells (Jurkat) for 24h and retsimulated or not with LPS for anaother 24h. MDDCs were then isolated from T cells using magnetic negative selection on CADM1 expression.
Samples from 3 independent experiment performed using MDDCs generated from monocytes isolated from 3 independent blood donors (identified as 118, 155 and 156) were subjected to RNA extraction and gene expression profiling by RNA sequencing.
Comparative gene expression profiling analysis of RNAseq data from MDDCs cultured with (i) control jurkat cells for 24h (A118_1, A155_1, A156_1) and restimulated for additional 24h with LPS (AL118_4, AL155_4, AL156_4), (ii) HTLV-1 infected cells (C91PL : B118_2, B155_2, B156_2 or C8166 : C118_3, C155_3, C156_3) and restimulated for additional 24h with LPS (BL118_5, BL155_5, BL156_5, or CL118_6, CL155_6, CL156_6)
|
| |
|
| Contributor(s) |
Carcone A, Mortreux F, Alais S, Mathieu C, Journo C, Dutartre H |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
| |
| Submission date |
May 07, 2024 |
| Last update date |
Sep 05, 2024 |
| Contact name |
franck mortreux |
| E-mail(s) |
franck.mortreux@ens-lyon.fr
|
| Organization name |
oncovirology and Biotherapies, UMR5239, LBMC
|
| Street address |
46 allee d'Italie
|
| City |
lyon |
| ZIP/Postal code |
69000 |
| Country |
France |
| |
|
| Platforms (1) |
| GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
|
| Samples (18)
|
|
| Relations |
| BioProject |
PRJNA1108877 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE266976_read_counts_matrix.csv.gz |
4.1 Mb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
|
|
|
|
 |
Less...
More...