The Role of Dendritic Cells and Monocytes in HIV Infection

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Background

Dendritic cells (DCs) and monocytes play an integral role in the pathogenesis of Human Immunodeficiency Virus (HIV). Myeloid DCs (mDCs) are typically widely disseminated in the body, including the blood, and interact closely with T cells in lymphoid tissues. The primary role of mDCs is in the processing of tissue antigens from the periphery and subsequent presentation to lymphocytes predominantly in lymphoid tissues. During HIV infection, mDC frequencies decline, and their levels are not completely restored by anti-retroviral therapy (ART). Monocyte and DC subset distribution is altered in the presence of HIV infection and monocyte/macrophage activation is associated with increased risk of all-cause mortality in both ART-treated and untreated HIV infected individuals.

A combination of approaches including in vitro, ex vivo and animal model-based studies during HIV infection have demonstrated the roles of DCs and monocytes in (i) viral spread; (ii) the establishment of latency; (iii) ongoing immune activation and (iv) clinical outcomes. Using in vitro models, it has been previously shown that the close interaction of mDC with resting CD4+ T cells leads to the transfer of HIV to CD4+ T cells as well as to the induction of latency following HIV-1 integration in circulating proliferating T cells. Recent studies using humanized myeloid-only mice (MoM) have indicated a shift to monocytes and dendritic cells as a dominant HIV reservoir in the absence of CD4+ T cells. However, the precise mechanisms underlying: (i) DC–HIV interactions that occur in vivo in relation to viral dissemination; (ii) viral latent reservoir establishment and/or (iii) maintenance remain unclear and are areas under investigation. Recent transcriptional- and proteomic-based reexamination of DC and monocyte ontogeny in steady-state, and sub-population plasticity in inflammatory conditions, calls for new studies addressing how DCs are altered in the presence of HIV infection as well as how the administration of ART impacts on the functions and proportions of DC and monocyte subsets. Research that enhances our understanding of DC and monocytes in HIV pathogenesis has the potential to (i) identify novel HIV therapies to eradicate viral reservoirs; (ii) to dampen pathological immune activation as well as (iii) to identify targets for DC vaccination strategies.

In this Research Topic, we welcome the submission of (i) Original Research; (ii) Methods; (iii) Protocols; and (iv) Clinical Trial articles that cover the following sub-topics:

1. The role of mDCs and monocytes in HIV latency.
2. mDC and monocyte ontogeny and subset distribution during HIV infection.
3. Mechanisms and studies of direct HIV Infection of mDC and monocyte subsets.
4. mDC and Monocytes in HIV-associated immune activation and clinical outcomes.

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