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Review
. 2018 Apr 19:9:805.
doi: 10.3389/fimmu.2018.00805. eCollection 2018.

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

Rajnish S Dave  1 , Pooja Jain  2 , Siddappa N Byrareddy  1
Affiliations
Review

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

Rajnish S Dave et al. Front Immunol. .

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.

Keywords: T follicular helper cells; central nervous system; cervical lymph nodes; combined antiretroviral therapy; follicular dendritic cells; human immunodeficiency virus; simian immunodeficiency virus; viral reservoirs.

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Figures

Figure 1
Figure 1
Schematic representation of the central nervous system (CNS)-associated meningeal lymphatic system and the human immunodeficiency virus (HIV) reservoir in the cervical lymph nodes (CLNs). (A) The functional meningeal lymphatic vessels drain cerebrospinal fluid (CSF). T cells and antigen-presenting cells migrate with the CSF along the nasal lymphatic pathways through the cribriform plate to access the CLNs. (B) CSF enters the CLN via the afferent lymphatic vessel and exits through the efferent lymphatic vessels. Germinal center (GC) is located within the B-cell follicle. The follicular dendritic cells (FDCs) are located within the light zone of the GC. (C) Within the CLNs, HIV infects T follicular helper precursor cells, which subsequently express CXCR5 and migrate to the light zone. As depicted in the inset, CD21 interacts with C3d on HIV surface. This interaction results in HIV acquisition by the FDCs. Majority of the FDC associated HIV cycles through the endosomal compartment.
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