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Cell Syst. 2019 Feb 27;8(2):109-121.e6. doi: 10.1016/j.cels.2019.01.001. Epub 2019 Feb 13.

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

Author information

1
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel.
2
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel; Systems Biology Group, Center for Bioinformatics, Biostatistics, and Integrative Biology (C3BI) and USR 3756, Institut Pasteur CNRS, Paris 75015, France; Sorbonne Universite, Complexite du vivant, F-75005 Paris, France.
3
Malaghan Institute of Medical Research, Wellington 6201, New Zealand; Department of Pathology and Molecular Medicine, University of Otago Wellington, Wellington 6201, New Zealand.
4
Life Sciences Core Facilities, Weizmann Institute of Science, Rehovot 76100, Israel.
5
Malaghan Institute of Medical Research, Wellington 6201, New Zealand.
6
Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
7
Systems Biology Group, Center for Bioinformatics, Biostatistics, and Integrative Biology (C3BI) and USR 3756, Institut Pasteur CNRS, Paris 75015, France.
8
Malaghan Institute of Medical Research, Wellington 6201, New Zealand. Electronic address: fronchese@malaghan.org.nz.
9
Department of Immunology, Weizmann Institute of Science, Rehovot 76100, Israel. Electronic address: ido.amit@weizmann.ac.il.

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.

KEYWORDS:

IFN-γ; NK cells; T cell polarization; antigen-presenting cells; cell-cell communication; dendritic cells; innate immune cells; lymph node; monocytes; single-cell RNA-seq

PMID:
30772378
DOI:
10.1016/j.cels.2019.01.001

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