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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
Trans-dominant cellular inhibition of DC-SIGN-mediated HIV-1 transmission
Li Wu1, Thomas D Martin, Yoon-Chi Han
1Model Development Section, HIV Drug Resistance Program, National Cancer Institute at Frederick, National Institutes of Health, Frederick, Maryland 21702, USA. liwu@ncifcrf.gov
Insights
Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells is cell-type dependent and requires cell-cell contact. The cellular environment can negatively regulate this DC-SIGN-mediated HIV-1 transmission.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells occurs at the infectious synapse.
- The relationship between the infectious synapse and the immunological synapse is unclear.
- Human B cells expressing DC-SIGN efficiently transmit HIV-1 to CD4+ T cells.
Purpose of the Study:
- To investigate if K562 cells, lacking key immunological synapse molecules, can mediate DC-SIGN-mediated HIV-1 transmission (DMHT).
- To understand the role of cell-cell contact and cellular milieu in DMHT.
Main Methods:
- Utilized K562 and Raji cell lines engineered to express DC-SIGN.
- Assessed HIV-1 transmission efficiency to CD4+ T cells.
- Investigated the impact of co-culture and cell-cell contact on DMHT.
Main Results:
- DMHT requires cell-cell contact.
- K562/DC-SIGN cells showed inefficient HIV-1 transmission compared to Raji/DC-SIGN cells.
- Co-culture with K562 cells impaired DMHT, indicating negative regulation by the cellular milieu.
Conclusions:
- DC-SIGN-mediated HIV-1 transmission is cell type-dependent and requires cell-cell contact.
- The cellular environment can negatively regulate HIV-1 transmission mediated by DC-SIGN.
Background:
Dendritic cell (DC) transmission of human immunodeficiency virus (HIV) to CD4+ T cells occurs across a point of cell-cell contact referred to as the infectious synapse. The relationship between the infectious synapse and the classically defined immunological synapse is not currently understood. We have recently demonstrated that human B cells expressing exogenous DC-SIGN, DC-specific intercellular adhesion molecule-3 (ICAM-3)-grabbing nonintegrin, efficiently transmit captured HIV type 1 (HIV-1) to CD4+ T cells. K562, another human cell line of hematopoietic origin that has been extensively used in functional analyses of DC-SIGN and related molecules, lacks the principal molecules involved in the formation of immunological synaptic junctions, namely major histocompatibility complex (MHC) class II molecules and leukocyte function-associated antigen-1 (LFA-1). We thus examined whether K562 erythroleukemic cells could recapitulate efficient DC-SIGN-mediated HIV-1 transmission (DMHT).
Results:
Here we demonstrate that DMHT requires cell-cell contact. Despite similar expression of functional DC-SIGN, K562/DC-SIGN cells were inefficient in the transmission of HIV-1 to CD4+ T cells when compared with Raji/DC-SIGN cells. Expression of MHC class II molecules or LFA-1 on K562/DC-SIGN cells was insufficient to rescue HIV-1 transmission efficiency. Strikingly, we observed that co-culture of K562 cells with Raji/DC-SIGN cells impaired DMHT to CD4+ T cells. The K562 cell inhibition of transmission was not directly exerted on the CD4+ T cell targets and required contact between K562 and Raji/DC-SIGN cells.
Conclusions:
DMHT is cell type dependent and requires cell-cell contact. We also find that the cellular milieu can negatively regulate DC-SIGN transmission of HIV-1 in trans.
