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.
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Change history
20 December 2019
"An amendment to this paper has been published and can be accessed via a link at the top of the paper."
20 December 2019
"An amendment to this paper has been published and can be accessed via a link at the top of the paper."
20 December 2019
"An amendment to this paper has been published and can be accessed via a link at the top of the paper."
20 December 2019
"An amendment to this paper has been published and can be accessed via a link at the top of the paper."
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Acknowledgements
The work was supported by INSERM, Ligue contre le Cancer, Ministere des affaires Etrangeres, Partenariat Curien Franco-Ukrainien “Dnipro” and The State Fund for Fundamental Research of Ukraine, National Academy of Sciences of Ukraine. Olga Romanets-Korbut was supported by FEBS Summer and Collaborative Fellowships, Bourse de Gouvernement Francais and AccueilDoc from Region Rhone Alpes. Authors thank to Dr T.B.H. Geijtenbeek (University of Amsterdam) for generous gift of AZN-D1 mAb and Dr D. Gerlier and members of the CIRI-INSERM-U1111 group “Immunobiology of viral infections” for their help in the achievement of this study.
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Romanets-Korbut, O., Kovalevska, L., Seya, T. et al. Measles virus hemagglutinin triggers intracellular signaling in CD150-expressing dendritic cells and inhibits immune response. Cell Mol Immunol 13, 828–838 (2016). https://doi.org/10.1038/cmi.2015.55
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DOI: https://doi.org/10.1038/cmi.2015.55
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