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Stem-cell Based Engineered Immunity Against HIV Infection in the Humanized Mouse Model
Published on: July 2, 2016
Activated CD34-derived Langerhans cells mediate transinfection with human immunodeficiency virus
Kelly M Fahrbach1, Sheila M Barry, Seyoum Ayehunie
1Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611-3008, USA.
Insights
Activated Langerhans cells (LCs), a type of dendritic cell (DC), can transmit human immunodeficiency virus (HIV) to other cells. This finding suggests LCs may play a role in HIV sexual transmission, especially when inflammation is present.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Langerhans cells (LCs) are dendritic cells (DCs) found in epidermal and mucosal tissues.
- LCs are strategically positioned to be among the first cells to encounter human immunodeficiency virus (HIV) during sexual transmission.
Purpose of the Study:
- To investigate the role of Langerhans cells (LCs) in human immunodeficiency virus (HIV) transinfection.
- To determine if LCs can facilitate the transmission of HIV to target cells and understand the mechanisms involved.
Main Methods:
- Purification of LCs from CD34(+)-derived dendritic cells (DCs).
- Activation of purified LCs.
- Observation of virion trafficking within LCs using microscopy, analyzing intracellular compartments and markers like langerin and CD1a.
- Assessment of the transinfection capability of activated LCs.
Main Results:
- Purified LCs, after activation, can facilitate the transinfection of target cells with HIV.
- HIV virions are found within an intracellular compartment in LCs, containing tetraspanins, langerin, and CD1a.
- HIV trafficking in LCs resembles that in mature monocyte-derived DCs and is dependent on the cell's activation state.
Conclusions:
- Activated Langerhans cells (LCs) can mediate HIV transinfection.
- The intracellular trafficking of HIV in LCs is similar to that in mature DCs and is influenced by LC activation.
- LCs may contribute to increased HIV transmission, particularly in the context of inflammatory conditions like sexually transmitted infections.
Abstract:
Langerhans cells (LCs) are a subset of dendritic cells (DCs) that reside within epidermal and mucosal tissue. Because of their location, LCs are potentially the first cells to encounter human immunodeficiency virus (HIV) during sexual transmission. We report that LCs purified from CD34(+)-derived DCs can facilitate the transinfection of target cells but only after activation. Virions were observed in an intracellular compartment that contains several tetraspanins, in addition to the unique LC markers langerin and CD1a. This reveals that the trafficking of HIV within LCs is reminiscent of that which occurs in mature monocyte-derived DCs and that it varies with the activation state of the cell. The observation that activated LCs can mediate transinfection suggests a potential role for these cells in the known increase in HIV transmission associated with sexually transmitted infections that would cause inflammation of the genital lining.
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