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Development and Functional Characterization of Murine Tolerogenic Dendritic Cells
Published on: May 18, 2018
Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10
Anna Chan1, Margaret Baird1, Andrew A Mercer1
1Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Abstract:
Orf virus (ORFV) is a parapoxvirus that infects sheep, goats and man. In humans, the virus induces acute, pustular skin lesions that can develop into a progressive disease. Humans are susceptible to reinfection with ORFV and rare cases of persistent infection have been reported. ORFV encodes several immunomodulators, including a homologue of interleukin-10 (ORFV IL-10), that may explain these phenomena. The immunosuppressive effects of ORFV IL-10 on immature human dendritic cells (DCs) cultured from blood-derived monocytes (MoDCs) were investigated. MoDCs exposed simultaneously to lipopolysaccharide and ORFV IL-10 showed enhanced ovalbumin-FITC uptake and reduced IL-12 expression, indicating inhibition of maturation. Moreover, ORFV IL-10 inhibited the upregulation of DC cell-surface activation and maturation markers MHC II, CD80, CD83 and CD86 and inhibited the capacity of MoDCs to activate CD4(+) T cells in an oxidative mitogenesis assay. These findings suggest that ORFV IL-10 may influence the development of acquired immunity in humans by impairing DC function.
Insights
Orf virus (ORFV) IL-10 suppresses human dendritic cell (DC) maturation and function. This impairs the ability of DCs to activate T cells, potentially affecting human immunity during ORFV infection.
Area of Science:
- Immunology
- Virology
- Dermatology
Background:
- Orf virus (ORFV) is a parapoxvirus causing skin lesions in sheep, goats, and humans.
- ORFV can cause persistent and recurrent infections in humans.
- ORFV encodes immunomodulatory proteins, including an interleukin-10 homolog (ORFV IL-10).
Purpose of the Study:
- To investigate the immunosuppressive effects of ORFV IL-10 on human dendritic cells (DCs).
- To determine how ORFV IL-10 influences DC maturation and function.
Main Methods:
- Human monocyte-derived dendritic cells (MoDCs) were cultured.
- MoDCs were treated with lipopolysaccharide (LPS) and ORFV IL-10.
- DC maturation markers (MHC II, CD80, CD83, CD86), IL-12 expression, and T cell activation capacity were assessed.
Main Results:
- ORFV IL-10 inhibited LPS-induced MoDC maturation.
- Enhanced ovalbumin-FITC uptake and reduced IL-12 expression indicated impaired maturation.
- ORFV IL-10 suppressed key DC activation markers and reduced T cell activation capacity.
Conclusions:
- ORFV IL-10 significantly impairs human dendritic cell function.
- This impairment may contribute to the persistent and recurrent infections observed in humans.
- ORFV IL-10's effects on DCs could influence the development of adaptive immunity during ORFV infection.
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