Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10.
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.
Chan
Anna
A
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Baird
Margaret
M
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Mercer
Andrew A
AA
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
Fleming
Stephen B
SB
Department of Microbiology and Immunology, University of Otago, PO Box 56, Dunedin, New Zealand.
D015703:Antigens, CD / Q000096:biosynthesis; D018122:B7-1 Antigen / Q000096:biosynthesis; D051940:B7-2 Antigen / Q000096:biosynthesis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002454:Cell Differentiation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D016753:Interleukin-10 / Q000378:metabolism / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear; D008213:Lymphocyte Activation / Q000187:drug effects; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009923:Orf virus / Q000378:metabolism*; D000097802:CD83 Antigen
D015703:Antigens, CD; D018122:B7-1 Antigen; D051940:B7-2 Antigen; D007136:Immunoglobulins; D016753:Interleukin-10; D018664:Interleukin-12; D008562:Membrane Glycoproteins; D000097802:CD83 Antigen