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

Rajnish S. Dave, Pooja Jain, Siddappa N. Byrareddy

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.