Follicular Dendritic Cells of Lymph Nodes as Human Immunodeficiency Virus/Simian Immunodeficiency Virus Reservoirs and Insights on Cervical Lymph Node

Abstract

A hallmark feature of follicular dendritic cells (FDCs) within the lymph nodes (LNs) is their ability to retain antigens and virions for a prolonged duration. FDCs in the cervical lymph nodes (CLNs) are particularly relevant in elucidating human immunodeficiency virus (HIV)-1 infection within the cerebrospinal fluid (CSF) draining LNs of the central nervous system. The FDC viral reservoir in both peripheral LN and CLN, like the other HIV reservoirs, contribute to both low-level viremia and viral resurgence upon cessation or failure of combined antiretroviral therapy (cART). Besides prolonged virion retention on FDCs in LNs and CLNs, the suboptimal penetration of cART at these anatomical sites is another factor contributing to establishing and maintaining this viral reservoir. Unlike the FDCs within the peripheral LNs, the CLN FDCs have only recently garnered attention. This interest in CLN FDCs has been driven by detailed characterization of the meningeal lymphatic system. As the CSF drains through the meningeal lymphatics and nasal lymphatics via the cribriform plate, CLN FDCs may acquire HIV after capturing them from T cells, antigen-presenting cells, or cell-free virions. In addition, CD4+ T follicular helper cells within the CLNs are productively infected as a result of acquiring the virus from the FDCs. In this review, we outline the underlying mechanisms of viral accumulation on CLN FDCs and its potential impact on viral resurgence or achieving a cure for HIV infection.

Expanded Circulating Follicular Dendritic Cells Facilitate Immune Responses in Chronic HBV Infection

“…Recent studies have reported the critical role of FDCs in chronic infectious diseases. Importantly, FDCs are a critical HIV reservoir where FDCs-trapped HIV persists for long periods, resulting in the perpetuation and reignition of the disease [29][30][31]. FDCs also play an essential role in autoimmune disorders, which frequently display follicles with ICs-bearing FDCs, autoreactive GCs, and ongoing a nity maturation [32,33].…”

Expanded circulating follicular dendritic cells facilitate immune responses in chronic HBV infection

“…Recent studies have reported the critical role of FDCs in chronic infectious diseases. Importantly, FDCs are a critical HIV reservoir in which FDC-trapped HIV persists for long periods, resulting in the perpetuation and reignition of the disease [31][32][33]. FDCs also play an essential role in autoimmune disorders, which frequently display follicles with ICs-bearing FDCs, autoreactive GCs, and ongoing a nity maturation [34,35].…”

Astrocytes, HIV and the Glymphatic System: A Disease of Disrupted Waste Management?

“…As described above, CSF and ISF exchange occurs in the peri-venous space and ISF is then transported from the brain to the cervical lymph nodes ( Figure 2 ; Iliff et al, 2013 ). Cervical lymph nodes (CLNs) are a group of lymph nodes in the neck region that are located adjacent to the cervical region of the spinal cord near the sternocleidomastoid muscle (Dave et al, 2018a ). The glymphatic and meningeal systems function as a waste removal pathway by connecting the CNS to the CLNs (Benveniste et al, 2017 ).…”

“…T cells and antigen-presenting cells (APCs) that are present within the CNS drain via the lymphatic path into the CLNs (Benveniste et al, 2017 ). CLNs contain follicular dendritic cells (FDCs) which can retain antigens for a prolonged duration allowing them to potentially act as a reservoir for HIV (Sabri et al, 2016 ; Dave et al, 2018a ). FDCs are important for immune function as they allow for germinal center formation, long term immune recovery (Dave et al, 2018a , b ) and may contribute significantly to immune system response to the virus, the viral reservoir and escape.…”

“…CLNs contain follicular dendritic cells (FDCs) which can retain antigens for a prolonged duration allowing them to potentially act as a reservoir for HIV (Sabri et al, 2016 ; Dave et al, 2018a ). FDCs are important for immune function as they allow for germinal center formation, long term immune recovery (Dave et al, 2018a , b ) and may contribute significantly to immune system response to the virus, the viral reservoir and escape. Importantly, given the intimate connection between glymphatic drainage and CLNs, the potential role of CLNs in glymphatic impairment and HIV infection should be considered.…”