Dynamics of macrophage polarization support Salmonella persistence in a whole living organism
- LPHI, CNRS, Université de Montpellier, France
- The Barcelona Institute of Science and Technology, Spain
- Université Paris-Saclay, CEA, CNRS, France
- Université de Montpellier, CNRS, INSERM, France
- Université de Montpellier, CNRS, INSERM, Montpellier France, France
- 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.
-
Dynamic changes of macrophage polarization during Salmonella infection in zebrafishNCBI Gene Expression Omnibus, GSE224985.
Article and author information
Author details
Pablo Loza-Alvarez
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.
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.
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.
Metrics
-
- 2,379
- views
-
- 287
- downloads
-
- 2
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Dynamics of macrophage polarization support Salmonella persistence in a whole living organism
eLife 13:e89828.
https://doi.org/10.7554/eLife.89828
Further reading
-
- Biochemistry and Chemical Biology
- Microbiology and Infectious Disease
In the bacterium M. smegmatis, an enzyme called MftG allows the cofactor mycofactocin to transfer electrons released during ethanol metabolism to the electron transport chain.
-
- Microbiology and Infectious Disease
Bacterial regional demonstration after global dissemination is an essential pathway for selecting distinct finesses. However, the evolution of the resistome during the transition to endemicity remains unaddressed. Using the most comprehensive whole-genome sequencing dataset of Salmonella enterica serovar Gallinarum (S. Gallinarum) collected from 15 countries, including 45 newly recovered samples from two related local regions, we established the relationship among avian-specific pathogen genetic profiles and localization patterns. Initially, we revealed the international transmission and evolutionary history of S. Gallinarum to recent endemicity through phylogenetic analysis conducted using a spatiotemporal Bayesian framework. Our findings indicate that the independent acquisition of the resistome via the mobilome, primarily through plasmids and transposons, shapes a unique antimicrobial resistance profile among different lineages. Notably, the mobilome-resistome combination among distinct lineages exhibits a geographical-specific manner, further supporting a localized endemic mobilome-driven process. Collectively, this study elucidates resistome adaptation in the endemic transition of an avian-specific pathogen, likely driven by the localized farming style, and provides valuable insights for targeted interventions.
