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Published on: November 22, 2011
Mucosal dendritic cells and immunodeficiency viruses
1Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA. popem@rockvax.rockefeller.edu
Insights
Dendritic cells (DCs) and T cells support human immunodeficiency virus type 1 (HIV-1) replication in skin and mucosal tissues. This DC-T cell interaction is crucial for virus growth, regardless of viral subtype or tropism.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cells (DCs) play a role in human immunodeficiency virus type 1 (HIV-1) pathogenesis.
- Skin and mucosal tissues are key sites for HIV-1 infection and transmission.
Purpose of the Study:
- To investigate the role of dendritic cells (DCs) and T cells in HIV-1 replication.
- To determine if DC-T cell interactions support virus growth in a skin-mucosal model.
Main Methods:
- Utilized skin explants as a model for mucosal tissues.
- Co-cultured dendritic cells (DCs) and T cells from human and macaque sources.
- Assessed HIV-1 and simian immunodeficiency virus (SIV) replication in these co-cultures.
Main Results:
- HIV-1 replicated efficiently in the DC-T cell milieu of skin explants, forming syncytia.
- Virus replication occurred irrespective of HIV-1 subtype, syncytium-inducing capacity, or tropism.
- Similar DC-T cell interactions supported simian immunodeficiency virus (SIV) replication in macaques.
- Active virus replication in both human and monkey systems required the presence of both DCs and T cells.
Conclusions:
- Dendritic cells (DCs) and T cells are essential for HIV-1 replication in skin and mucosal tissues.
- DC-T cell syncytia are a site of active HIV-1 replication.
- Further research using the macaque model will explore DC roles in HIV transmission and spread.
Abstract:
Dendritic cells [DCs] have been implicated in the pathogenesis of human immunodeficiency virus type 1 (HIV-1). When skin was used as a model for mucosae, the cutaneous DC-T cell milieu allowed the growth of HIV-1 and much of the newly produced virus could be detected in multinucleated DC-T cell syncytia. Such virus replication occurs irrespective of the genetic subtype, the syncytium- and non-syncytium-inducing capacities of the viruses, and whether they are classified as T cell- or macrophage-tropic. Similar DC-syncytia have been identified within the mucosal surfaces of the tonsillar tissue of HIV-1-infected persons. More recently, it was demonstrated that DC-T cell mixtures from the skin, mucosae, and blood of healthy macaques similarly support the replication of simian immunodeficiency virus. In both the human and monkey systems, active virus replication requires the presence of both DCs and T cells. Further studies using the macaque model are underway to elucidate the role of DCs in the transmission and spread of HIV infection.
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