Measles virus interacts with human SLAM receptor on dendritic cells to cause immunosuppression.
Measles virus (MV) infects dendritic cells (DCs) resulting in immunosuppression. Human DCs express two MV receptors: CD46 and human signaling lymphocyte activation molecule (hSLAM); thus, the role played by either alone is unclear. Because wild-type (wt) MV uses hSLAM receptor preferentially, we dissected the molecular basis of MV-DC interaction and resultant immunosuppression through the hSLAM receptor by creating transgenic (tg) mice expressing hSLAM on DCs. After infection with wt MV, murine splenic DCs expressing hSLAM receptor had less B7-1, B7-2, CD40, MHC class I, and MHC class II molecules on their surfaces and displayed an increased rate of apoptosis when compared to uninfected DCs. Further, MV-infected DCs failed to stimulate allogeneic T cells and inhibited mitogen-dependent T-cell proliferation. Individual expression of human SLAM, interferon alpha/beta receptor, tumor necrosis factor-alpha, and lymphotoxin-alpha or beta from T cells was not required for MV-infected DCs to inhibit the proliferation of T cells.
Hahm
Bumsuk
B
Division of Virology, Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Arbour
Nathalie
N
Oldstone
Michael B A
MB
D000818:Animals; D015703:Antigens, CD; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007136:Immunoglobulins / Q000235:genetics / Q000378:metabolism*; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008457:Measles; D008459:Measles virus / Q000472:pathogenicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011956:Receptors, Cell Surface; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D019076:Transgenes
D015703:Antigens, CD; D006023:Glycoproteins; D007136:Immunoglobulins; D011956:Receptors, Cell Surface; D011991:Receptors, Virus; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1