Accumulation of functionally immature myeloid dendritic cells in lymph nodes of rhesus macaques with acute pathogenic simian immunodeficiency virus infection

Authors

  • Viskam Wijewardana,

    1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA
    Current affiliation:
    1. Department of Advanced Pathobiology, Graduate School of Life and Environmental Sciences, Osaka Prefecture University, Osaka, Japan
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  • Anthea L. Bouwer,

    1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA
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  • Kevin N. Brown,

    1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA
    Current affiliation:
    1. Division of Therapeutic Proteins, Center for Drug Evaluation and Research, Food and Drug Administration, Bethesda, MD, USA
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  • Xiangdong Liu,

    1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA
    Current affiliation:
    1. Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA
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  • Simon M. Barratt-Boyes

    Corresponding author
    1. Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA, USA
    2. Department of Infectious Diseases and Microbiology, University of Pittsburgh, Pittsburgh, PA, USA
    3. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA
    • Correspondence: Simon M. Barratt-Boyes, University of Pittsburgh, 9046 Biomedical Science Tower 3, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA.

      Email: smbb@pitt.edu

      Senior author: Simon M. Barratt-Boyes

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Summary

Myeloid dendritic cells (mDC) are key mediators of innate and adaptive immunity to virus infection, but the impact of HIV infection on the mDC response, particularly early in acute infection, is ill-defined. We studied acute pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques to address this question. The mDC in blood and bone marrow were depleted within 12 days of intravenous infection with SIVmac251, associated with a marked proliferative response. In lymph nodes, mDC were apoptotic, activated and proliferating, despite normal mDC numbers, reflecting a regenerative response that compensated for mDC loss. Blood mDC had increased expression of MHC class II, CCR7 and CD40, whereas in lymph nodes these markers were significantly decreased, indicating that acute infection induced maturation of mDC in blood but resulted in accumulation of immature mDC in lymph nodes. Following SIV infection, lymph node mDC had an increased capacity to secrete tumour necrosis factor-α upon engagement with a Toll-like receptor 7/8 ligand that mimics exposure to viral RNA, and this was inversely correlated with MHC class II and CCR7 expression. Lymph node mDC had an increased ability to capture and cleave soluble antigen, confirming their functionally immature state. These data indicate that acute SIV infection results in increased mDC turnover, leading to accumulation in lymph nodes of immature mDC with an increased responsiveness to virus stimulation.

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