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Generation of Human Monocyte-derived Dendritic Cells from Whole Blood
Published on: December 24, 2016
Cytokine production by human herpesvirus 8-infected dendritic cells
Heather R Hensler1, Giovanna Rappocciolo, Charles R Rinaldo
1Department of Infectious Diseases and Microbiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA.
Insights
Human herpesvirus 8 (HHV-8) infection impairs dendritic cell (DC) maturation and antigen presentation. HHV-8-infected DCs show altered cytokine profiles, potentially skewing immune responses toward Th2.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Human herpesvirus 8 (HHV-8) is associated with various malignancies.
- Dendritic cells (DCs) are crucial for initiating adaptive immune responses.
- Previous studies indicated HHV-8-infected DCs exhibit incomplete maturation and impaired antigen presentation.
Purpose of the Study:
- To investigate the impact of HHV-8 infection on cytokine production by dendritic cells (DCs).
- To understand how HHV-8 manipulates DC function through cytokine modulation.
- To determine the implications of altered cytokine profiles for immune responses.
Main Methods:
- Dendritic cells (DCs) were infected with Human herpesvirus 8 (HHV-8).
- Cytokine expression levels (IL-6, TNF-alpha, MIP-1alpha, MIP-1beta, RANTES, IL-12p40) were measured post-infection using techniques like ELISA or RT-PCR.
- Analysis of bioactive IL-12p70 in supernatants was performed.
Main Results:
- Expression of IL-6, TNF-alpha, MIP-1alpha, MIP-1beta, RANTES, and IL-12p40 was detected early post-infection, peaking at 15-24 hours.
- TNF-alpha remained elevated throughout the 72-hour observation period.
- While IL-12p40 increased, bioactive IL-12p70 was notably absent in supernatants of infected DCs.
Conclusions:
- HHV-8 infection significantly alters cytokine production in dendritic cells (DCs).
- The observed cytokine profile suggests a deliberate manipulation by HHV-8 to promote a Th2-biased immune response.
- These findings provide insights into the immune evasion strategies employed by HHV-8.
Abstract:
We have shown previously that human herpesvirus 8 (HHV-8)-infected dendritic cells (DCs) undergo incomplete maturation and have a defective antigen-presenting function. Here, we examined the effects of HHV-8 infection on cytokine production, which is critical to the function of DCs. We detected expression of interleukin (IL)-6, tumour necrosis factor (TNF)-alpha, macrophage inflammatory protein (MIP)-1alpha, MIP-1beta, RANTES and IL-12p40 from 2 to 6 h post-infection, and these peaked by 15-24 h. Expression of these factors decreased 24-48 h post-infection, with the exception of TNF-alpha which remained high throughout the entire 72 h. Interestingly, while IL-12p40 expression increased post-infection, bioactive IL-12p70 was not detected in the supernatants. These results suggest an intentional skewing of cytokine production in HHV-8-infected DCs towards induction of a Th2 response.
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