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FDC:TFH Interactions within Cervical Lymph Nodes of SIV-Infected Rhesus Macaques

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Abstract

Cerebrospinal fluid (CSF) drains via the lymphatic drainage pathway. This lymphatic pathway connects the central nervous system (CNS) to the cervical lymph node (CLN). As the CSF drains to CLN via the dural and nasal lymphatics, T cells and antigen presenting cells pass along the channels from the subarachnoid space through the cribriform plate. Human immunodeficiency virus (HIV) may also egress from the CNS along this pathway. As a result, HIV egressing from the CNS may accumulate within the CLN. Towards this objective, we analyzed CLNs isolated from rhesus macaques that were chronically-infected with simian immunodeficiency virus (SIV). We detected significant accumulation of SIV within the CLNs. SIV virion trapping was observed on follicular dendritic cells (FDCs) localized within the follicular regions of CLNs. In addition, SIV antigens formed immune complexes when FDCs interacted with B cells within the germinal centers. Subsequent interaction of these B cells with CD4+ T follicular helper cells (TFHs) resulted in infection of the latter. Of note, 73% to 90% of the TFHs cells within CLNs were positive for SIV p27 antigen. As such, it appears that not only do the FDCs retain SIV they also transmit them (via B cells) to TFHs within these CLNs. This interaction results in infection of TFHs in the CLNs. Based on these observations, we infer that FDCs within the CLNs have a novel role in SIV entrapment with implications for viral trafficking.

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Funding

These studies have been funded in part with NINDS R01 NS097147 to PJ and NIAID R01 AI113883; R21 AI114415; and R21 MH11345501 to SB.

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Author notes

  1. Rajnish S. Dave and Ravi K. Sharma equally contributed to this work.

Authors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA

    Rajnish S. Dave & Siddappa N. Byrareddy

  2. Department of Microbiology and Immunology, and the Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, 2900 Queen Lane, Suite G47A, Philadelphia, PA, 19129, USA

    Ravi K. Sharma, Artinder P. Nehra, Zafar K. Khan, Brian Wigdahl & Pooja Jain

  3. Advanced Eye Center, Post Graduate Institute of Medical Education and Research, Chandigarh, India

    Ravi K. Sharma

  4. Division of Infectious Disease and HIV Medicine, Department of Medicine, Drexel University College of Medicine, Philadelphia, PA, USA

    Roshell R. Muir & Elias Haddad

  5. Department of Pathology & Laboratory Medicine, School of Medicine and Emory Vaccine Center, Emory University, Atlanta, GA, USA

    Sanjeev Gumber & Aftab A. Ansari

  6. New Iberia Research Center, University of Louisiana at Lafayette, New Iberia, LA, USA

    Francois Villinger

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  1. Rajnish S. Dave
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Correspondence to Siddappa N. Byrareddy or Pooja Jain.

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This article does not contain any studies with human participants performed by any of the authors. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. For the detailed ethical statement please refer to materials and methods.

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Electronic supplementary material

Supplementary Fig. 1

(A) Representative figure from center of BCF showing antigen-harboring FDCs. The center was relatively devoid of CD20+B cells (green) and had plenty of CD35+FDCs (yellow), which showed the colocalization with p27 (red) inside the BCF. There were relatively fewer PD-1hi expressing TFH cells (blue) also. (B) The numbers of TFH cells were more towards the peripheral regions of BCF. This is significant considering the ability of TFH cells to migrate from lymph nodes into circulation. (PDF 1316 kb)

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Dave, R.S., Sharma, R.K., Muir, R.R. et al. FDC:TFH Interactions within Cervical Lymph Nodes of SIV-Infected Rhesus Macaques. J Neuroimmune Pharmacol 13, 204–218 (2018). https://doi.org/10.1007/s11481-017-9775-0

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