title: Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response.
abstract: Measles virus (MV) is highly contagious pathogen, which causes a profound immunosuppression, resulting in high infant mortality. This virus infects dendritic cells (DCs) following the binding of MV hemagglutinin (MV-H) to CD150 receptor and alters DC functions by a mechanism that is not completely understood. We have analyzed the effect of MV-H interaction with CD150-expressing DCs on the DC signaling pathways and consequent phenotypic and functional changes in the absence of infectious context. We demonstrated that contact between CD150 on human DCs and MV-H expressed on membrane of transfected CHO cells was sufficient to modulate the activity of two major regulatory pathways of DC differentiation and function: to stimulate Akt and inhibit p38 MAPK phosphorylation, without concomitant ERK1/2 activation. Furthermore, interaction with MV-H decreased the expression level of DC activation markers CD80, CD83, CD86, and HLA-DR and strongly downregulated IL-12 production but did not modulate IL-10 secretion. Moreover, contact with MV-H suppressed DC-mediated T-cell alloproliferation, demonstrating profound alteration of DC maturation and functions. Finally, engagement of CD150 by MV-H in mice transgenic for human CD150 decreased inflammatory responses, showing the immunosuppressive effect of CD150-MV-H interaction in vivo. Altogether, these results uncover novel mechanism of MV-induced immunosuppression, implicating modulation of cell signaling pathways following MV-H interaction with CD150-expressing DCs and reveal anti-inflammatory effects of CD150 stimulation.
authors.affiliation: CIRI, International Center for Infectiology Research, IbIV team, Université de Lyon, Lyon, France.|R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine.
authors.forename: Olga
authors.initials: O
authors.lastname: Romanets-Korbut
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine.
authors.forename: Larysa M
authors.initials: LM
authors.lastname: Kovalevska
authors.affiliation: Department of Microbiology and Immunology, Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Seya
authors.affiliation: R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NASU, Kyiv, Ukraine.
authors.forename: Svetlana P
authors.initials: SP
authors.lastname: Sidorenko
authors.affiliation: CIRI, International Center for Infectiology Research, IbIV team, Université de Lyon, Lyon, France.|Inserm, U1111, Lyon, France.|CNRS, UMR5308, Lyon, France.|Université Lyon 1, Lyon, France.|Ecole Normale Supérieure de Lyon, Lyon, France.
authors.forename: Branka
authors.initials: B
authors.lastname: Horvat
mesh_terms: D000818:Animals; D002460:Cell Line; D003713:Dendritic Cells / Q000276:immunology*; D006388:Hemagglutinins / Q000276:immunology*; D006801:Humans; D007109:Immunity; D007249:Inflammation / Q000473:pathology; D042541:Intracellular Space / Q000378:metabolism*; D008459:Measles virus / Q000276:immunology*; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D010641:Phenotype; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1 / Q000378:metabolism*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D006388:Hemagglutinins; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D051057:Proto-Oncogene Proteins c-akt; D048051:p38 Mitogen-Activated Protein Kinases