Skip to Main content Skip to Navigation
Journal articles

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

Ronnie Blecher-Gonen 1 Pierre Bost 1, 2, 3 Kerry Hilligan 4 Eyal David 1 Tomer Meir Salame 1 Elsa Roussel 4 Lisa Connor 4 Johannes Mayer 4 Keren Bahar Halpern 1 Beáta Tóth 1 Shalev Itzkovitz 1 Benno Schwikowski 2 Franca Ronchese 1 Ido Amit 1
1 Weizmann Institute of Science [Rehovot, Israël]
2 Biologie systémique - Systems Biology
Institut Pasteur [Paris], CNRS - Centre National de la Recherche Scientifique : USR 3756
3 ED 515 - Complexité du vivant
4 Malaghan Institute of Medical Research [Wellington, New Zealand]
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
Document type :
Journal articles
Complete list of metadata
https://hal-pasteur.archives-ouvertes.fr/pasteur-02965324
Contributor : Benno Schwikowski Connect in order to contact the contributor
Submitted on : Tuesday, October 13, 2020 - 10:59:54 AM
Last modification on : Friday, December 3, 2021 - 11:43:30 AM

Links full text

openaccess

Identifiers

Collections

PASTEUR | CNRS | SORBONNE-UNIVERSITE | SU-TI

Citation

Ronnie Blecher-Gonen, Pierre Bost, Kerry Hilligan, Eyal David, Tomer Meir Salame, et al.. Single-Cell Analysis of Diverse Pathogen Responses Defines a Molecular Roadmap for Generating Antigen-Specific Immunity. Cell Systems, Elsevier, 2019, 8 (2), pp.109-121.e6. ⟨10.1016/j.cels.2019.01.001⟩. ⟨pasteur-02965324⟩

Export

BibTeX TEI DC DCterms EndNote

Share

Metrics

Les métriques sont temporairement indisponibles