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Interleukin-10 contributes to reservoir establishment and persistence in SIV-infected macaques treated with antiretroviral therapy

  1. Author:
    Harper, Justin
    Ribeiro, Susan P
    Chan, Chi Ngai
    Aid, Malika
    Deleage,Claire
    Micci, Luca
    Pino, Maria
    Cervasi, Barbara
    Raghunathan, Gopalan
    Rimmer, Eric
    Ayanoglu, Gulesi
    Wu, Guoxin
    Shenvi, Neeta
    Barnard, Richard Jo
    Del Prete,Greg
    Busman-Sahay, Kathleen
    Silvestri, Guido
    Kulpa, Deanna A
    Bosinger, Steven E
    Easley, Kirk
    Howell, Bonnie J
    Gorman, Dan
    Hazuda, Daria J
    Estes, Jacob D
    Sekaly, Rafick-Pierre
    Paiardini, Mirko

  2. Author Address

    Yerkes National Primate Research Center, Emory University, Atlanta, United States of America., Department of Pathology, Case Western Reserve University, Cleveland, United States of America., Vaccine and Gene Therapy Institute, Oregon Health & Science University, Beaverton, United States of America., Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Boston, United States of America., AIDS and Cancer Virus Program, Leidos Biomedical Research, Frederick National Laboratory for Cancer Research, Frederick, United States of America., Department of Discovery Oncology, Merck & Co., Inc., Boston, United States of America., Department of Discovery Biologics, Merck & Co., Inc., South San Francisco, United States of America., Department of Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Merck & Co., Inc., South San Francisco, United States of America., Department of Infectious Disease, Merck & Co., Inc., West Point, United States of America., Department of Biostatistics and Bioinformatics, Emory University, Atlanta, United States of America., AIDS and Cancer Virus Program, Leidos Biomedical Research, Inc., Frederick National Laboratory for Cancer, Frederick, United States of America., Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, United States of America., Vaccine & Gene Therapy Institute, Oregon Health & Science University, Beaverton, United States of America., Department of Pathology, Emory University, Atlanta, United States of America., Department of Pathology and Laboratory Medicine, Emory Univerisity, Atlanta, United States of America.,
    1. Year: 2022
    2. Date: Mar 01
    3. Epub Date: 2022 03 01
  2. Journal: The Journal of Clinical Investigation
    1. 132
    2. 8
  4. Type of Article: Article
  5. Article Number: e155251
  1. Abstract:

    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) were induced by infection and not normalized with ART. During chronic infection, plasma IL-10 and transcriptomic signatures of IL-10 signaling were 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. In ART-treated RMs, cells harboring SIV-DNA by DNAscope were preferentially found in the LN B-cell follicle in proximity to IL-10. Finally, we demonstrated that the in vivo neutralization of soluble IL-10 in ART-treated, SIV-infected macaques reduced B cell follicle maintenance and by extension LN memory CD4+ T-cells, including TFH and those 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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External Sources

  1. View Full Text
  2. DOI: 10.1172/JCI155251
  3. PMID: 35230978
  4. View record in Web of Science®
  5. WOS: 000793215200003
  6. PII : 155251

Library Notes

  1. Fiscal Year: FY2021-2022
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