Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model

Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threa...

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Main Authors: Jonas Kjellin, Maria Pränting, Frauke Bach, Roshan Vaid, Bart Edelbroek, Zhiru Li, Marc P. Hoeppner, Manfred Grabherr, Ralph R. Isberg, Monica Hagedorn, Fredrik Söderbom
Format: Article
Language:English
Published: BMC 2019-12-01
Series:BMC Genomics
Subjects:
Online Access:https://doi.org/10.1186/s12864-019-6269-x
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spelling doaj-f8916d4c0cc247a18e96cca2e49dbd872020-12-13T12:18:09ZengBMCBMC Genomics1471-21642019-12-0120111810.1186/s12864-019-6269-xInvestigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host modelJonas Kjellin0Maria Pränting1Frauke Bach2Roshan Vaid3Bart Edelbroek4Zhiru Li5Marc P. Hoeppner6Manfred Grabherr7Ralph R. Isberg8Monica Hagedorn9Fredrik Söderbom10Department of Cell and Molecular Biology, Uppsala UniversityDepartment of Cell and Molecular Biology, Uppsala UniversitySection Parasitology, Bernhard Nocht Institute for Tropical MedicineDepartment of Cell and Molecular Biology, Uppsala UniversityDepartment of Cell and Molecular Biology, Uppsala UniversityDepartment of Molecular Biology and Microbiology, Tufts University School of MedicineDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Medical Biochemistry and Microbiology, Uppsala UniversityDepartment of Molecular Biology and Microbiology, Tufts University School of MedicineSection Parasitology, Bernhard Nocht Institute for Tropical MedicineDepartment of Cell and Molecular Biology, Uppsala UniversityAbstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.https://doi.org/10.1186/s12864-019-6269-xHost-pathogenInfectionHigh-throughput sequencingMycobacteriaLegionellaDictyostelium discoideum
collection DOAJ
language English
format Article
sources DOAJ
author Jonas Kjellin
Maria Pränting
Frauke Bach
Roshan Vaid
Bart Edelbroek
Zhiru Li
Marc P. Hoeppner
Manfred Grabherr
Ralph R. Isberg
Monica Hagedorn
Fredrik Söderbom
spellingShingle Jonas Kjellin
Maria Pränting
Frauke Bach
Roshan Vaid
Bart Edelbroek
Zhiru Li
Marc P. Hoeppner
Manfred Grabherr
Ralph R. Isberg
Monica Hagedorn
Fredrik Söderbom
Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
BMC Genomics
Host-pathogen
Infection
High-throughput sequencing
Mycobacteria
Legionella
Dictyostelium discoideum
author_facet Jonas Kjellin
Maria Pränting
Frauke Bach
Roshan Vaid
Bart Edelbroek
Zhiru Li
Marc P. Hoeppner
Manfred Grabherr
Ralph R. Isberg
Monica Hagedorn
Fredrik Söderbom
author_sort Jonas Kjellin
title Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
title_short Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
title_full Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
title_fullStr Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
title_full_unstemmed Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
title_sort investigation of the host transcriptional response to intracellular bacterial infection using dictyostelium discoideum as a host model
publisher BMC
series BMC Genomics
issn 1471-2164
publishDate 2019-12-01
description Abstract Background During infection by intracellular pathogens, a highly complex interplay occurs between the infected cell trying to degrade the invader and the pathogen which actively manipulates the host cell to enable survival and proliferation. Many intracellular pathogens pose important threats to human health and major efforts have been undertaken to better understand the host-pathogen interactions that eventually determine the outcome of the infection. Over the last decades, the unicellular eukaryote Dictyostelium discoideum has become an established infection model, serving as a surrogate macrophage that can be infected with a wide range of intracellular pathogens. In this study, we use high-throughput RNA-sequencing to analyze the transcriptional response of D. discoideum when infected with Mycobacterium marinum and Legionella pneumophila. The results were compared to available data from human macrophages. Results The majority of the transcriptional regulation triggered by the two pathogens was found to be unique for each bacterial challenge. Hallmark transcriptional signatures were identified for each infection, e.g. induction of endosomal sorting complexes required for transport (ESCRT) and autophagy genes in response to M. marinum and inhibition of genes associated with the translation machinery and energy metabolism in response to L. pneumophila. However, a common response to the pathogenic bacteria was also identified, which was not induced by non-pathogenic food bacteria. Finally, comparison with available data sets of regulation in human monocyte derived macrophages shows that the elicited response in D. discoideum is in many aspects similar to what has been observed in human immune cells in response to Mycobacterium tuberculosis and L. pneumophila. Conclusions Our study presents high-throughput characterization of D. discoideum transcriptional response to intracellular pathogens using RNA-seq. We demonstrate that the transcriptional response is in essence distinct to each pathogen and that in many cases, the corresponding regulation is recapitulated in human macrophages after infection by mycobacteria and L. pneumophila. This indicates that host-pathogen interactions are evolutionary conserved, derived from the early interactions between free-living phagocytic cells and bacteria. Taken together, our results strengthen the use of D. discoideum as a general infection model.
topic Host-pathogen
Infection
High-throughput sequencing
Mycobacteria
Legionella
Dictyostelium discoideum
url https://doi.org/10.1186/s12864-019-6269-x
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