Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity
| Autor: | Pierre Bost, Eyal David, Ido Amit, Ronnie Blecher-Gonen, Franca Ronchese, Tomer-Meir Salame, Johannes U Mayer, Keren Bahar Halpern, Kerry L. Hilligan, Beáta Tóth, Benno Schwikowski, Shalev Itzkovitz, Lisa M. Connor, Elsa Roussel |
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| Přispěvatelé: | Weizmann Institute of Science [Rehovot, Israël], Biologie systémique - Systems Biology, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Sorbonne Université (SU), Malaghan Institute of Medical Research [Wellington, New Zealand], I.A. is supported by the Chan Zuckerberg Initiative, the HHMI International Scholar award, the European Research Council Consolidator Grant (ERC-COG) 724471-HemTree2.0, the Israel Science Foundation (703/15), the Ernest and Bonnie Beutler Research Program of Excellence in Genomic Medicine, the Helen and Martin Kimmel award for innovative investigation, a Minerva Stiftung research grant, the Israeli Ministry of Science, Technology, and Space, the David and Fela Shapell Family Foundation, the NeuroMac DFG/Transregional Collaborative Research Center Grant, and the Abramson Family Center for Young Scientists. I.A. is the incumbent of the Alan and Laraine Fischer Career Development Chair. This work was also funded by an Independent Research Organization grant from the Health Research Council of New Zealand to the Malaghan Institute (grant number HRC14/1003). K.L.H. was supported by a Ph.D. scholarship from the University of Otago Wellington, Wellington. P.B. was supported by a Ph.D. scholarship from the Ecole Normale Supérieure, Paris., We thank members of the I.A. and F.R. labs as well as Alice Balfourier for discussions. We thank Tal Bigdari for artwork., European Project: 724471,ERC-2016-COG,HemTree2.0(2017), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Cell type
Chemokine Histology NK cells Pathology and Forensic Medicine Mice 03 medical and health sciences 0302 clinical medicine Immune system Single-cell analysis Immunity [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases Animals Humans antigen-presenting cells MESH: Animals dendritic cells Antigen-presenting cell innate immune cells IFN-γ MESH: Mice cell-cell communication 030304 developmental biology Systems immunology 0303 health sciences Innate immune system single-cell RNA-seq MESH: Humans biology Cell Biology lymph node Immunity Innate 3. Good health T cell polarization Immunology biology.protein [SDV.IMM]Life Sciences [q-bio]/Immunology MESH: Immunity Innate Single-Cell Analysis monocytes 030217 neurology & neurosurgery MESH: Single-Cell Analysis |
| Zdroj: | Cell Systems Cell Systems, Elsevier, 2019, 8 (2), pp.109-121.e6. ⟨10.1016/j.cels.2019.01.001⟩ Cell Systems, 2019, 8 (2), pp.109-121.e6. ⟨10.1016/j.cels.2019.01.001⟩ |
| ISSN: | 2405-4712 2405-4720 |
| DOI: | 10.1016/j.cels.2019.01.001⟩ |
| Popis: | International audience; The immune system generates pathogen-tailored responses. The precise innate immune cell types and pathways that direct robust adaptive immune responses have not been fully characterized. By using fluorescent pathogens combined with massively parallel single-cell RNA-seq, we comprehensively characterized the initial 48 h of the innate immune response to diverse pathogens. We found that across all pathogens tested, most of the lymph node cell types and states showed little pathogen specificity. In contrast, the rare antigen-positive cells displayed pathogen-specific transcriptional programs as early as 24 h after immunization. In addition, mycobacteria activated a specific NK-driven IFNγ response. Depletion of NK cells and IFNγ showed that IFNγ initiated a monocyte-specific signaling cascade, leading to the production of major chemokines and cytokines that promote Th1 development. Our systems immunology approach sheds light on early events in innate immune responses and may help further development of safe and efficient vaccines. |
| Databáze: | OpenAIRE |
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