Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity

Ronnie Blecher-Gonen; Pierre Bost; Kerry L. Hilligan; Eyal David; Tomer Meir Salame; Elsa Roussel; Lisa M. Connor; Johannes U. Mayer; Keren Bahar Halpern; Beata Toth; Shalev Itzkovitz; Benno Schwikowski; Franca Ronchese; Ido Amit

doi:https://doi.org/10.1016/j.cels.2019.01.001

Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity

Ronnie Blecher-Gonen, Pierre Bost, Kerry L. Hilligan, Eyal David, Tomer Meir Salame, Elsa Roussel, Lisa M. Connor, Johannes U. Mayer, Keren Bahar Halpern, Beata Toth, Shalev Itzkovitz, Benno Schwikowski, Franca Ronchese, Ido Amit

Weizmann Institute of Science

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	109-121.e6
Number of pages	19
Journal	Cell Systems
Volume	8
Issue number	2
DOIs	https://doi.org/10.1016/j.cels.2019.01.001
State	Published - 27 Feb 2019

All Science Journal Classification (ASJC) codes

Pathology and Forensic Medicine
Histology
Cell Biology

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https://doi.org/10.1016/j.cels.2019.01.001

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Blecher-Gonen, R., Bost, P., Hilligan, K. L., David, E., Salame, T. M., Roussel, E., Connor, L. M., Mayer, J. U., Halpern, K. B., Toth, B., Itzkovitz, S., Schwikowski, B., Ronchese, F., & Amit, I. (2019). Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity. Cell Systems, 8(2), 109-121.e6. https://doi.org/10.1016/j.cels.2019.01.001

@article{6c7bee1e72214b03a43df44f649dc7f2,

title = "Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity",

abstract = "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.",

author = "Ronnie Blecher-Gonen and Pierre Bost and Hilligan, {Kerry L.} and Eyal David and Salame, {Tomer Meir} and Elsa Roussel and Connor, {Lisa M.} and Mayer, {Johannes U.} and Halpern, {Keren Bahar} and Beata Toth and Shalev Itzkovitz and Benno Schwikowski and Franca Ronchese and Ido Amit",

note = "We thank members of the I.A. and F.R. labs as well as Alice Balfourier for discussions. We thank Tal Bigdari for artwork. 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 Sup{\'e}rieure, Paris.",

year = "2019",

month = feb,

day = "27",

doi = "https://doi.org/10.1016/j.cels.2019.01.001",

language = "الإنجليزيّة",

volume = "8",

pages = "109--121.e6",

journal = "Cell Systems",

issn = "2405-4712",

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Blecher-Gonen, R, Bost, P, Hilligan, KL, David, E, Salame, TM, Roussel, E, Connor, LM, Mayer, JU, Halpern, KB, Toth, B, Itzkovitz, S, Schwikowski, B, Ronchese, F & Amit, I 2019, 'Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity', Cell Systems, vol. 8, no. 2, pp. 109-121.e6. https://doi.org/10.1016/j.cels.2019.01.001

TY - JOUR

T1 - Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity

AU - Blecher-Gonen, Ronnie

AU - Bost, Pierre

AU - Hilligan, Kerry L.

AU - David, Eyal

AU - Salame, Tomer Meir

AU - Roussel, Elsa

AU - Connor, Lisa M.

AU - Mayer, Johannes U.

AU - Halpern, Keren Bahar

AU - Toth, Beata

AU - Itzkovitz, Shalev

AU - Schwikowski, Benno

AU - Ronchese, Franca

AU - Amit, Ido

N1 - We thank members of the I.A. and F.R. labs as well as Alice Balfourier for discussions. We thank Tal Bigdari for artwork. 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.

PY - 2019/2/27

Y1 - 2019/2/27

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85061775708&partnerID=8YFLogxK

U2 - https://doi.org/10.1016/j.cels.2019.01.001

DO - https://doi.org/10.1016/j.cels.2019.01.001

M3 - مقالة

SN - 2405-4712

VL - 8

SP - 109-121.e6

JO - Cell Systems

JF - Cell Systems

IS - 2

ER -

Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity

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