Dynamics of macrophage polarization support Salmonella persistence in a whole living organism

  1. Jade Leiba  Is a corresponding author
  2. Tamara Sipka
  3. Christina Begon-Pescia
  4. Matteo Bernardello
  5. Sofiane Tairi
  6. Lionello Bossi
  7. Anne-Alicia Gonzalez
  8. Xavier Mialhe
  9. Emilio Gualda
  10. Pablo Loza-Alvarez
  11. Anne Blanc-Potard
  12. Georges Lutfalla
  13. Mai E Nguyen-Chi  Is a corresponding author
  1. LPHI, CNRS, Université de Montpellier, France
  2. The Barcelona Institute of Science and Technology, Spain
  3. Université Paris-Saclay, CEA, CNRS, France
  4. Université de Montpellier, CNRS, INSERM, France
  5. Université de Montpellier, CNRS, INSERM, Montpellier France, France
  6. LIPH, CNRS, INSERM, Univ Montpellier, France

Abstract

Numerous intracellular bacterial pathogens interfere with macrophage function, including macrophage polarization, to establish a niche and persist. However, the spatiotemporal dynamics of macrophage polarization during infection within host remain to be investigated. Here, we implement a model of persistent Salmonella Typhimurium infection in zebrafish, which allows visualization of polarized macrophages and bacteria in real time at high-resolution. While macrophages polarize toward M1-like phenotype to control early infection, during later stages, Salmonella persists inside non-inflammatory clustered macrophages. Transcriptomic profiling of macrophages showed a highly dynamic signature during infection characterized by a switch from pro-inflammatory to anti-inflammatory/pro-regenerative status and revealed a shift in adhesion program. In agreement with this specific adhesion signature, macrophage trajectory tracking identifies motionless macrophages as a permissive niche for persistent Salmonella. Our results demonstrate that zebrafish model provides a unique platform to explore, in a whole organism, the versatile nature of macrophage functional programs during bacterial acute and persistent infections.

Data availability

The raw sequencing data is available in the NCBI GEO database under accession number: GSE224985, https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE224985.Figure 7 - Source Data 1 contains the numerical data used to generate the figures.Other data that support the findings are openly available from the public repository Zenodo at https://zenodo.org/records/10409519, at the publication date.

The following data sets were generated

Article and author information

Author details

  1. Jade Leiba

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    For correspondence
    jade.leiba@umontpellier.fr
    Competing interests
    The authors declare that no competing interests exist.
  2. Tamara Sipka

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Christina Begon-Pescia

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  4. Matteo Bernardello

    ICFO - Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Spain
    Competing interests
    The authors declare that no competing interests exist.
  5. Sofiane Tairi

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  6. Lionello Bossi

    Institute for Integrative Biology of the Cell-I2BC, Université Paris-Saclay, CEA, CNRS, Gif-sur-Yvette, France
    Competing interests
    The authors declare that no competing interests exist.
  7. Anne-Alicia Gonzalez

    MGX-Montpellier GenomiX, Université de Montpellier, CNRS, INSERM, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Xavier Mialhe

    MGX-Montpellier GenomiX, Université de Montpellier, CNRS, INSERM, Montpellier France, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Emilio Gualda

    ICFO - Institute of Photonic Sciences, The Barcelona Institute of Science and Technology, Castelldefels, Spain
    Competing interests
    The authors declare that no competing interests exist.
  10. Pablo Loza-Alvarez

    ICFO-Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Castelldefels, Spain
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3129-1213
  11. Anne Blanc-Potard

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Georges Lutfalla

    DIMNP, LIPH, CNRS, INSERM, Univ Montpellier, Montpellier, France
    Competing interests
    The authors declare that no competing interests exist.
  13. Mai E Nguyen-Chi

    LPHI, CNRS, Université de Montpellier, Montpellier, France
    For correspondence
    mai-eva.nguyen-chi@umontpellier.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2672-2426

Funding

Horizon 2020 Framework Programme (MSCA-ITN ImageInLife Grant Agreement n{degree sign} 721537)

  • Pablo Loza-Alvarez
  • Georges Lutfalla

Horizon 2020 Framework Programme (MSCA-ITN Inflanet Grant Agreement n{degree sign} 955576)

  • Mai E Nguyen-Chi

Agence Nationale de la Recherche (ANR-19-CE15-0005-01,MacrophageDynamics)

  • Mai E Nguyen-Chi

Region Occitanie (REPERE « INFLANET »)

  • Mai E Nguyen-Chi

Spanish Ministerio de Economía y Competitividad (CEX2019-000910-S)

  • Matteo Bernardello
  • Emilio Gualda emilio.jose.gualda@upc.edu.
  • Pablo Loza-Alvarez

MINECO/FEDER (RYC-2015-17935)

  • Matteo Bernardello
  • Emilio Gualda emilio.jose.gualda@upc.edu.
  • Pablo Loza-Alvarez

Horizon 2020 Framework Programme (Laserlab-Europe GA no. 871124)

  • Pablo Loza-Alvarez

Fundació Privada Cellex

  • Matteo Bernardello
  • Emilio Gualda emilio.jose.gualda@upc.edu.
  • Pablo Loza-Alvarez

Fundación Mig-Puig

  • Matteo Bernardello
  • Emilio Gualda emilio.jose.gualda@upc.edu.
  • Pablo Loza-Alvarez

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Sophie Helaine, Harvard Medical School, United States

Ethics

Animal experimentation: Animal experimentation procedures were carried out according to the European Union guidelines for handling of laboratory animals (https://ec.europa.eu/environment/chemicals/lab_animals/index_en.htm) and were approved by the Comité d'Ethique pour l'Expérimentation Animale under reference CEEA-LR- B4-172-37 and APAFIS #36309-2022040114222432 V2. Fish husbandry, embryo collection, animal experimentations, handling, and euthanasia were performed at the University of Montpellier, LPHI/CNRS UMR5295, by authorized staff. All experimentations were performed under tricain (Ethyl 3-aminobenzoate) anesthesia, and every effort was made to minimize suffering. Euthanasia was performed using an anesthetic overdose of tricain.

Version history

  1. Preprint posted: May 10, 2023 (view preprint)
  2. Received: June 2, 2023
  3. Accepted: January 14, 2024
  4. Accepted Manuscript published: January 15, 2024 (version 1)
  5. Version of Record published: January 31, 2024 (version 2)

Copyright

© 2024, Leiba et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Jade Leiba
  2. Tamara Sipka
  3. Christina Begon-Pescia
  4. Matteo Bernardello
  5. Sofiane Tairi
  6. Lionello Bossi
  7. Anne-Alicia Gonzalez
  8. Xavier Mialhe
  9. Emilio Gualda
  10. Pablo Loza-Alvarez
  11. Anne Blanc-Potard
  12. Georges Lutfalla
  13. Mai E Nguyen-Chi
(2024)
Dynamics of macrophage polarization support Salmonella persistence in a whole living organism
eLife 13:e89828.
https://doi.org/10.7554/eLife.89828

Share this article

https://doi.org/10.7554/eLife.89828

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