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Lymphocyte Isolation from Human Skin for Phenotypic Analysis and Ex Vivo Cell Culture
Published on: April 8, 2016
Orf virus IL-10 reduces monocyte, dendritic cell and mast cell recruitment to inflamed skin
Jared R Bennett1, Zabeen Lateef1, Stephen B Fleming1
1Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
Abstract:
Orf virus (ORFV) is a zoonotic parapoxvirus that causes pustular dermatitis of sheep, and occasionally humans. Despite causing sustained infections, ORFV induces only a transient increase in pro-inflammatory signalling and the trafficking of innate immune cells within the skin seems to be impaired. An explanation for this tempered response to ORFV infection may lie in its expression of a homolog of the anti-inflammatory cytokine, interleukin (IL)-10. Using a murine model in which inflammation was induced by bacterial lipopolysaccharide, we examined the effects of the ORFV-IL-10 protein on immune cell trafficking to and from the skin. ORFV-IL-10 limited the recruitment of blood-derived Gr-1(int)/CD11b(int) monocytes, CD11c(+ve)/MHC-II(+ve) dendritic cells and c-kit(+ve)/FcεR1(+ve) mature mast cells into inflamed skin. ORFV-IL-10 also suppressed the activation of CD11c(+ve)/MHC-II(+ve) dendritic cells within the skin, reducing their trafficking to the draining lymph node. These findings suggest that expression of IL-10 by ORFV may contribute to the impaired trafficking of innate immune cells within infected skin.
Insights
Orf virus (ORFV) produces an interleukin-10 (IL-10) homolog that impairs innate immune cell trafficking to the skin. This viral IL-10 limits monocyte, dendritic cell, and mast cell recruitment, potentially explaining ORFV
Area of Science:
- Virology
- Immunology
- Dermatology
Background:
- Orf virus (ORFV), a zoonotic parapoxvirus, causes skin disease in sheep and humans.
- ORFV infections lead to transient inflammation and impaired innate immune cell trafficking in the skin.
- ORFV expresses a protein homologous to interleukin-10 (IL-10), an anti-inflammatory cytokine.
Purpose of the Study:
- To investigate the effect of ORFV-encoded IL-10 on immune cell trafficking in inflamed skin.
- To understand how ORFV-IL-10 influences the recruitment and activation of innate immune cells.
Main Methods:
- Utilized a murine model with lipopolysaccharide-induced skin inflammation.
- Administered ORFV-IL-10 to assess its impact on immune cell populations.
- Quantified immune cell recruitment (monocytes, dendritic cells, mast cells) and activation using flow cytometry.
Main Results:
- ORFV-IL-10 significantly limited the influx of monocytes, dendritic cells, and mast cells into inflamed skin.
- ORFV-IL-10 suppressed the activation of dendritic cells within the skin.
- Reduced dendritic cell activation led to decreased trafficking to draining lymph nodes.
Conclusions:
- ORFV-IL-10 plays a critical role in modulating the host immune response during infection.
- The viral IL-10 homolog contributes to impaired innate immune cell trafficking in ORFV-infected skin.
- This mechanism may allow ORFV to establish and maintain persistent infections by evading immune surveillance.
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