Impaired B cells survival upon production of inflammatory cytokines by HIV-1 exposed follicular dendritic cells

Sabri, Farideh; Prados, Alejandro; Muñoz-Fernández, Raquel; Lantto, Rebecka; Fernández-Rubio, Pablo; Nasi, Aikaterini; Amu, Sylvie; Albert, Jan; Olivares, Enrique G.; Chiodi, Francesca

doi:10.1186/s12977-016-0295-4

Cited by 11 publications

(11 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TNF-α produced by FDCs results in a significant increase in HIV replication when co-cultured with infected CD4 + T cells ( 28 ). Additionally, exposure of FDCs to HIV in vitro results in the production of cytokines that are unfavorable to B cell survival and antibody production ( 83 ).…”

Section: Follicular Dendritic Cellsmentioning

confidence: 99%

The B-Cell Follicle in HIV Infection: Barrier to a Cure

2018

View full text Add to dashboard Cite

The majority of HIV replication occurs in secondary lymphoid organs (SLOs) such as the spleen, lymph nodes, and gut-associated lymphoid tissue. Within SLOs, HIV RNA + cells are concentrated in the B-cell follicle during chronic untreated infection, and emerging data suggest that they are a major source of replication in treated disease as well. The concentration of HIV RNA + cells in the B-cell follicle is mediated by several factors. Follicular CD4 + T-cell subsets including T-follicular helper cells and T-follicular regulatory cells are significantly more permissive to HIV than extrafollicular subsets. The B cell follicle also contains a large reservoir of extracellular HIV virions, which accumulate on the surface of follicular dendritic cells (FDCs) in germinal centers. FDC-bound HIV virions remain infectious even in the presence of neutralizing antibodies and can persist for months or even years. Moreover, the B-cell follicle is semi-immune privileged from CTL control. Frequencies of HIV- and SIV-specific CTL are lower in B-cell follicles compared to extrafollicular regions as the majority of CTL do not express the follicular homing receptor CXCR5. Additionally, CTL in the B-cell follicle may be less functional than extrafollicular CTL as many exhibit the recently described CD8 T follicular regulatory phenotype. Other factors may also contribute to the follicular concentration of HIV RNA + cells. Notably, the contribution of NK cells and γδ T cells to control and/or persistence of HIV RNA + cells in secondary lymphoid tissue remains poorly characterized. As HIV research moves increasingly toward the development of cure strategies, a greater understanding of the barriers to control of HIV infection in B-cell follicles is critical. Although no strategy has as of yet proven to be effective, a range of novel therapies to address these barriers are currently being investigated including genetically engineered CTL or chimeric antigen receptor T cells that express the follicular homing molecule CXCR5, treatment with IL-15 or an IL-15 superagonist, use of bispecific antibodies to harness the killing power of the follicular CD8 + T cell population, and disruption of the follicle through treatments such as rituximab.

show abstract

Section: Follicular Dendritic Cellsmentioning

confidence: 99%

The B-Cell Follicle in HIV Infection: Barrier to a Cure

2018

View full text Add to dashboard Cite

show abstract

“…HIV production increases to twofold when viral particles are transferred from FDCs to susceptible CD4+ T cells ( 35 ). FDCs can secrete inflammatory cytokines ( 29 ) including TNF alpha and thereby contribute to enhanced transcription in the LNs ( 35 ).…”

Section: Key Cellular Players In the Clnmentioning

confidence: 99%

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

2018

View full text Add to dashboard Cite

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.

show abstract

“…Although the mechanisms are not fully elucidated yet, gradual histological alterations such as the deposition of collagen and non-amyloid substance may be associated with follicular involution at the end stage of HIV infection (17, 18). Exposure of follicular dendritic cells to HIV may create an inflammatory environment and lead to the impaired survival of follicular B cells (19). The magnitude of GC reactions in follicular hyperplasia or involution, if any, is closely linked to the regulation of follicular helper T (TFH) cells.…”

Section: Generation Of Follicular Hyperplasia/involutionmentioning

confidence: 99%

The Dynamics of T and B Cells in Lymph Node during Chronic HIV Infection: TFH and HIV, Unhappy Dance Partners?

2016

View full text Add to dashboard Cite

Although the dynamics of germinal center (GC) formation, follicular helper T (TFH) cell recruitment to B cell follicles within lymphoid organs, and changes of lymphoid tissue architecture in HIV/SIV infection have been documented, the underlying immunopathology remains unclear. Here, we summarize what is known regarding the kinetics of TFH cells and GC B cells during the course of infection as well as the potential immunopathological features associated with structural changes in the lymphoid compartment. This review also explores the implications of cell dynamics in the formation and maintenance of viral reservoirs in hyperplastic follicles of secondary lymphoid organs before and after viral suppressive antiretroviral therapy.

show abstract

Impaired B cells survival upon production of inflammatory cytokines by HIV-1 exposed follicular dendritic cells

Cited by 11 publications

References 38 publications

The B-Cell Follicle in HIV Infection: Barrier to a Cure

The B-Cell Follicle in HIV Infection: Barrier to a Cure

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

The Dynamics of T and B Cells in Lymph Node during Chronic HIV Infection: TFH and HIV, Unhappy Dance Partners?

Contact Info

Product

Resources

About