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| Status |
Public on Feb 09, 2022 |
| Title |
Interleukin-10 contributes to reservoir establishment and persistence in antiretroviral therapy-treated, SIV-infected macaques |
| Organism |
Macaca mulatta |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Interleukin (IL)-10 is an immunosuppressive cytokine that signals through STAT3 to regulate T follicular helper cell (TFH) differentiation and germinal center formation. In SIV-infected macaques, levels of IL-10 in plasma and lymph node (LN) are induced by infection and not normalized with ART. During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were significantly correlated with the cell-associated SIV-DNA content within LN CD4+ memory subsets, including TFH, and predicted the frequency of CD4+ TFH and their cell- associated SIV-DNA content during ART, respectively. Notably, in ART-treated RMs, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B-cell follicle in close proximity to IL-10. Finally, we demonstrate that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques significantly reduces B cell follicle maintenance and, by extension, cellular sites of viral persistence, including LN TFH and memory CD4+ T-cells expressing PD-1 and CTLA-4. Thus, these data support a role for IL-10 in maintaining a pool of target cells in lymphoid tissue that serve as a niche for viral persistence. Targeting IL-10 signaling to impair CD4+ T-cell survival and improve antiviral immune responses may represent a novel approach to limit viral persistence in ART-suppressed people living with HIV.
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| Overall design |
16 female Indian-origin, specific-pathogen-free (SPF) rhesus macaques were infected with SIVmac239 and at day 60 post-infection (p.i.) began a 5-drug, oral antiretroviral therapy. Starting at d60 and d203 p.i., seven RMs began 6-dose, weekly cycle of subcutaneous rhesus IL-21-IgFc (IL-21)
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| Contributor(s) |
Harper J, Ribeiro SP, Chan CN, Aid M, Deleage C, Micci L, Pino M, Cervasi B, Raghunathan G, Rimmer E, Ayanoglu G, Wu G, Shenvi N, Barnard RJ, Prete GD, Busman-Sahay K, Bosinger S, Easley K, Howell BJ, Gorman D, Hazuda DJ, Estes JD, Sekaly R, Paiardini M, Tharp GK |
| Citation(s) |
35230978 |
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| Submission date |
Feb 04, 2022 |
| Last update date |
Aug 07, 2023 |
| Contact name |
Gregory K Tharp |
| E-mail(s) |
gktharp@emory.edu
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| Phone |
404-727-7797
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| Organization name |
Yerkes National Primate Research Center
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| Department |
Developmental and Cognitive Neuroscience
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| Lab |
Genomics Core
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| Street address |
954 Gatewood Dr
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| City |
Atlanta |
| State/province |
GA |
| ZIP/Postal code |
30329-4208 |
| Country |
USA |
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| Platforms (2) |
| GPL20313 |
Illumina HiSeq 1000 (Macaca mulatta) |
| GPL23804 |
Illumina HiSeq 3000 (Macaca mulatta) |
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| Samples (59)
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| Relations |
| BioProject |
PRJNA803542 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196182_Raw_Read_Counts_Justin-2020-07-14.txt.gz |
1.4 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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