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Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10

Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand

Correspondence
Stephen Fleming
stephen.fleming{at}stonebow.otago.ac.nz

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.

A figure showing characterization of MoDCs and a table showing the effect of ORFV IL-10 on IL-12 production from MoDCs are available as supplementary material in JGV Online.

This article has been cited by other articles:

				S. B. Fleming, I. E. Anderson, J. Thomson, D. L. Deane, C. J. McInnes, C. A. McCaughan, A. A. Mercer, and D. M. Haig Infection with recombinant orf viruses demonstrates that the viral interleukin-10 is a virulence factor J. Gen. Virol., July 1, 2007; 88(7): 1922 - 1927. [Abstract] [Full Text] [PDF]

				L. Wise, C. McCaughan, C. K. Tan, A. A. Mercer, and S. B. Fleming Orf virus interleukin-10 inhibits cytokine synthesis in activated human THP-1 monocytes, but only partially impairs their proliferation J. Gen. Virol., June 1, 2007; 88(6): 1677 - 1682. [Abstract] [Full Text] [PDF]