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| Status |
Public on Feb 09, 2022 |
| Title |
Interleukin-10 regulates 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, which we propose acts as a determinant of HIV/SIV persistence. 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 |
Evaluation of the safety and bioactivity of IL-10 neutralization in SIV-infected rhesus macaques receiving short-term ART.
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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 |
| Citation(s) |
35230978 |
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| Submission date |
Feb 09, 2022 |
| Last update date |
May 12, 2022 |
| Contact name |
Dan Barouch |
| Organization name |
BIDMC
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| Department |
CVVR
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| Lab |
Barouch Lab
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| Street address |
3 Blackfan Circle
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL20313 |
Illumina HiSeq 1000 (Macaca mulatta) |
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| Samples (40)
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| Relations |
| BioProject |
PRJNA804895 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE196436_processedData_geo_feb8.csv.gz |
918.3 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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