Clemence Ngo, Camille Pierini-Malosse, Khalissa Rahmani, Michael Valente, Nils Collinet, Gilles Bessou, Capucine Guerry, Manon Fabregue, Solene Mathieu, Sarah Sharkaoui, Sophie Mazzoli, Amandine Sansoni, Frederic Fiore, Caroline Laprie, Lena Alexopoulou, Mauro Gaya, Claude Gregoire, Achille Broggi, Sarah Wurbel, Réjane Rua, Narjess Haidar, Pierre Milpied, Bertrand Escalière, Thien Phong Vu Manh, Mathieu Fallet, Lionel Chasson, Hien Tran, Thomas Baranek, Marc Le Bert, Bernard Malissen, Ana Zarubica, Marc Dalod, Elena Tomasello
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引用次数: 0
Abstract
Plasmacytoid dendritic cells (pDCs) are major producers of type I/III interferons. As interferons are crucial for antiviral defense, pDCs are assumed to play an essential role in this process; however, robust evidence supporting this dogma is scarce. Genetic or pharmacological manipulations that eliminate pDCs or disrupt their interferon production often affect other cells, confounding interpretation. Here, to overcome this issue, we engineered pDC-less mice that are specifically and constitutively devoid of pDCs by expressing diphtheria toxin under coordinated control of the Siglech and Pacsin1 genes, uniquely coexpressed in pDCs. pDC-less mice mounted protective immunity against systemic infection with mouse cytomegalovirus and showed higher survival and less lung immunopathology to intranasal infection with influenza virus and SARS-CoV-2. Thus, contrary to the prevailing dogma, we revealed that pDCs and their interferons are dispensable or deleterious during several viral infections. pDC-less mice will enable rigorously reassessing the roles of pDCs in health and disease.
期刊介绍:
Nature Immunology is a monthly journal that publishes the highest quality research in all areas of immunology. The editorial decisions are made by a team of full-time professional editors. The journal prioritizes work that provides translational and/or fundamental insight into the workings of the immune system. It covers a wide range of topics including innate immunity and inflammation, development, immune receptors, signaling and apoptosis, antigen presentation, gene regulation and recombination, cellular and systemic immunity, vaccines, immune tolerance, autoimmunity, tumor immunology, and microbial immunopathology. In addition to publishing significant original research, Nature Immunology also includes comments, News and Views, research highlights, matters arising from readers, and reviews of the literature. The journal serves as a major conduit of top-quality information for the immunology community.