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

• Type of Material: Conference Paper
• Authors: Rajnish S. Dave, University of Nebraska Medical Center; Ravi K. Sharma, Drexel University; Roshell R. Muir, Drexel University; Elias Haddad, Drexel University; Sanjeev Gumber, Emory University; Francois Villinger, University of Louisiana Lafayette; Artinder P. Nehra, Drexel University; Zafar K. Khan, Drexel University; Brian Wigdahl, Drexel University; Aftab A Ansari, Emory University; Siddappa N. Byrareddy, Emory University; Pooja Jain, Drexel University
• Language: English
• Date: 2018-06-01
• Publisher: Emory University Libraries
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2017, Springer Science+Business Media, LLC, part of Springer Nature.
• Final Published Version (URL): http://dx.doi.org/10.1007/s11481-017-9775-0
• Title of Journal or Parent Work: JOURNAL OF NEUROIMMUNE PHARMACOLOGY
• Volume: 13
• Issue: 2
• Start Page: 204
• End Page: 218
• Grant/Funding Information: These studies have been funded in part with NINDS R01 NS097147 to PJ and NIAID R01 AI113883; R21 AI114415; and R21 MH11345501 to SB.
• Keywords: Central nervous system (CNS); SIMIAN IMMUNODEFICIENCY VIRUS; CENTRAL-NERVOUS-SYSTEM; Neurosciences & Neurology; Human immunodeficiency virus (HIV); HIV-INFECTION; BLOOD-BRAIN-BARRIER; VIRAL PERSISTENCE; Follicular dendritic cells (FDCs); Life Sciences & Biomedicine; CD4+T follicular helper cells (TFHs); Science & Technology; T-CELLS; HELPER-CELLS; Simian immunodeficiency virus (SIV); EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; Pharmacology & Pharmacy; Neurosciences; CEREBROSPINAL-FLUID; FOLLICULAR DENDRITIC CELLS
• Research Categories: Biology, Neuroscience; Health Sciences, Immunology; Health Sciences, Pathology

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.