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Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
Published on: September 1, 2015
Identification of HIV transmitting CD11c+ human epidermal dendritic cells
Kirstie M Bertram1,2, Rachel A Botting1,2,3, Heeva Baharlou1,2
1Centre for Virus Research, The Westmead Institute for Medical Research, 176 Hawkesbury Road, Westmead, New South Wales, 2145, Australia.
Epidermal dendritic cells (DCs), not just Langerhans cells (LCs), are present in the skin. These CD11c+ DCs in anogenital skin are key players in HIV transmission to CD4 T cells.
Area of Science:
- Immunology
- Virology
- Dermatology
Background:
- Langerhans cells (LCs) were considered the sole mononuclear phagocyte population in the epidermis.
- Their role in pathogen detection and immune response initiation is established.
Purpose of the Study:
- To identify and characterize other mononuclear phagocyte populations in the epidermis.
- To investigate the role of these cells in HIV interaction and sexual transmission.
Main Methods:
- Transcriptional profiling of epidermal cell populations.
- Antigen-presenting cell efficiency assays.
- HIV interaction, uptake, replication, and transmission studies.
- Flow cytometry and cell sorting.
Main Results:
- Identified a CD11c+ dendritic cell (DC) population in the epidermis, transcriptionally similar to dermal cDC2.
- These epidermal CD11c+ DCs are more efficient antigen-presenting cells than LCs.
- Epidermal CD11c+ DCs are enriched in anogenital tissues, interact more with HIV, express higher CCR5, and are more efficient at HIV uptake, replication, and transmission to CD4 T cells.
- A CD33low cell population, similar to LCs, was identified but did not function as antigen-presenting cells or HIV targets.
Conclusions:
- Epidermal CD11c+ DCs, particularly in anogenital tissues, are critical for HIV sexual transmission.
- These cells represent a significant target for interventions aimed at preventing HIV transmission.
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