Human cytomegalovirus-derived protein UL18 alters the phenotype and function of monocyte-derived dendritic cells.
Human cytomegalovirus (HCMV) encodes the MHC class I-like molecule UL18, which binds with high affinity to the leukocyte Ig-like receptor-1 (LIR-1), an inhibitory receptor commonly expressed on myeloid cells and subsets of NK and T cells. The exact role of UL18 is not known, in particular in relation to its proposed role in HCMV immune escape. Given the ubiquitous expression of LIR-1 on dendritic cells (DCs), we hypothesized that UL18 may affect DC function. To study the effects of UL18 on DC, we made use of UL18 fusion proteins. We demonstrate that UL18 fusion proteins inhibit the chemotaxis of DCs. Furthermore, UL18 interfered with CD40 ligand-induced maturation of DCs, resulting in reduced allogeneic T cell proliferation. Finally, we demonstrate that UL18 proteins up-regulate the expression of the maturation marker CD83 on immature monocyte-derived DCs and induce cytokine production. The capacity of UL18 to affect the function and the phenotype of DCs suggests a novel role for this HCMV-derived protein.
Wagner
Claudia S
CS
Center for Infectious Medicine, Department of Medicine, Karolinska Institutet, Karolinska University Hospital Huddinge, 141 86 Stockholm, Sweden. claudia.wagner@ki.se
Walther-Jallow
Lilian
L
Buentke
Eva
E
Ljunggren
Hans-Gustaf
HG
Achour
Adnane
A
Chambers
Benedict J
BJ
D015703:Antigens, CD / Q000096:biosynthesis; D023201:CD40 Ligand / Q000276:immunology; D036022:Capsid Proteins / Q000276:immunology* / Q000494:pharmacology; D002465:Cell Movement / Q000276:immunology; D049109:Cell Proliferation; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D007136:Immunoglobulins / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D009000:Monocytes / Q000166:cytology; D010641:Phenotype; D011993:Recombinant Fusion Proteins / Q000276:immunology / Q000494:pharmacology; D013601:T-Lymphocytes / Q000276:immunology; D000097802:CD83 Antigen
D015703:Antigens, CD; D023201:CD40 Ligand; D036022:Capsid Proteins; D016207:Cytokines; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D000097802:CD83 Antigen; C079750:VP23 protein, Human herpesvirus 1