Mechanism of measles virus-induced suppression of inflammatory immune responses.
Measles virus (MV) causes profound immunosuppression, resulting in high infant mortality. The mechanisms are poorly understood, largely due to the lack of a suitable animal model. Here, we report that particular MV proteins, in the absence of MV replication, could generate a systemic immunosuppression in mice through two pathways: (1) via MV-nucleoprotein and its receptor FcgammaR on dendritic cells; and (2) via virus envelope glycoproteins and the MV-hemagglutinin cellular receptor, CD46. The effects comprise reduced hypersensitivity responses associated with impaired function of dendritic cells, decreased production of IL-12, and the loss of antigen-specific T cell proliferation. These results introduce a novel model for testing the immunosuppressive potential of anti-measles vaccines and reveal a specific mechanism of MV-induced modulation of inflammatory reactions.
Marie
J C
JC
INSERM U503, CERVI, Immunobiologie Fondamentale et Clinique, 69365, Lyon, France.
Kehren
J
J
Trescol-Biémont
M C
MC
Evlashev
A
A
Valentin
H
H
Walzer
T
T
Tedone
R
R
Loveland
B
B
Nicolas
J F
JF
Rabourdin-Combe
C
C
Horvat
B
B
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D003713:Dendritic Cells / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology; D004139:Dinitrofluorobenzene / Q000276:immunology; D004195:Disease Models, Animal; D006389:Hemagglutinins, Viral / Q000276:immunology*; D006433:Hemocyanins / Q000276:immunology; D006968:Hypersensitivity, Delayed / Q000139:chemically induced / Q000276:immunology; D007166:Immunosuppressive Agents / Q000276:immunology*; D018664:Interleukin-12 / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D008459:Measles virus / Q000276:immunology*; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000276:immunology*; D017452:Receptors, IgG / Q000276:immunology*; D014466:Ultraviolet Rays; D014760:Viral Fusion Proteins / Q000276:immunology*; D014764:Viral Proteins / Q000276:immunology*
D015703:Antigens, CD; D006389:Hemagglutinins, Viral; D007166:Immunosuppressive Agents; C497859:Mcp protein, mouse; D051916:Membrane Cofactor Protein; D008562:Membrane Glycoproteins; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D017452:Receptors, IgG; D014760:Viral Fusion Proteins; D014764:Viral Proteins; C032397:hemagglutinin protein G, measles virus; C058314:nucleoprotein, Measles virus; D018664:Interleukin-12; D006433:Hemocyanins; D004139:Dinitrofluorobenzene; C032808:keyhole-limpet hemocyanin