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Published on: May 4, 2015
Replication pattern of human immunodeficiency virus type 1 in mature Langerhans cells
B Ludewig1, J Holzmeister, M Gentile
1Department of Virology, Robert Koch-Institut, Berlin, Germany.
Insights
Mature Langerhans cells (mLC) can be infected by human immunodeficiency virus type 1 (HIV-1). These cells, found in lymph nodes as interdigitating cells (IDC), may serve as targets for HIV-1 infection.
Area of Science:
- Immunology
- Virology
- Dermatology
Background:
- Langerhans cells (LC) are skin-resident dendritic cells that mature into potent immunostimulatory interdigitating cells (IDC) in lymph nodes.
- Mature Langerhans cells (mLC) share phenotypic and functional similarities with IDC.
Purpose of the Study:
- To investigate the susceptibility of mLC to infection by different strains of human immunodeficiency virus type 1 (HIV-1).
- To understand the role of mLC and IDC in HIV-1 pathogenesis.
Main Methods:
- Purified mLC were cultured and characterized for surface molecule expression (MHC class I/II, CD40, CD80, CD86, CD4).
- mLC were infected with macrophagetropic (SF162) and lymphotropic (IIIB) HIV-1 strains.
- Virus replication, syncytia formation, and cytopathic effects were assessed.
- The influence of tumor necrosis factor alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) on infection was evaluated.
Main Results:
- mLC expressed high levels of immunostimulatory molecules and upregulated CD4 during cultivation.
- The macrophagetropic HIV-1 strain SF162 replicated more efficiently in mLC than the lymphotropic strain IIIB.
- Both HIV-1 strains induced syncytia, with SF162 causing a more rapid cytopathic effect.
- TNF-alpha enhanced HIV-1 production by improving cell viability, while GM-CSF had no significant effect.
Conclusions:
- Mature Langerhans cells are susceptible to HIV-1 infection.
- Interdigitating cells in lymph nodes may serve as target cells for HIV-1 in infected individuals.
- Cytokine modulation, particularly TNF-alpha, can influence HIV-1 replication in mLC.
Abstract:
Langerhans cells (LC), the dendritic antigen presenting cells of the skin, mature into potent immunostimulatory cells during migration to regional lymph nodes, where they are identified as interdigitating cells (IDC). Since mature Langerhans cells (mLC) resemble IDC in phenotype and immunostimulatory capacity, we examined whether these cells were susceptible to infection with macrophagetropic and lymphotropic strains of human immunodeficiency virus type 1 (HIV-1). Highly purified cell preparations of mLC migrating from human epidermis expressed high amounts of major histocompatibility complex (MHC) class I and II antigens and of the accessory molecules CD40, CD80 and CD86, indicative of the phenotype of potent immunostimulatory cells. CD4 expression was upregulated on mLC during cultivation, independent of the presence of tumour necrosis factor alpha (TNF-alpha) and granulocyte-macrophage colony-stimulating factor (GM-CSF) in the culture medium. The macrophagetropic HIV-1 strain SF162 replicated to higher titres in mLC than the lymphotropic strain IIIB. Both strains induced syncytia, with SF162 showing a more rapid cytopathic effect. Addition of TNF-alpha enhanced virus production, due to better cell viability under TNF-alpha treatment, whereas GM-CSF did not significantly influence viability of cells and replication pattern of the virus. These findings suggest that in the infected individual IDC in lymph nodes may function as target cells for HIV-1.
