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Investigation of th...
Investigation of the host transcriptional response to intracellular bacterial infection using Dictyostelium discoideum as a host model
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- Kjellin, Jonas (author)
- Uppsala universitet,Mikrobiologi
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- Pränting, Maria (author)
- Uppsala universitet,Institutionen för medicinska vetenskaper,Institutionen för cell- och molekylärbiologi
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- Bach, Frauke (author)
- Bernhard Nocht Inst Trop Med, Sect Parasitol, Hamburg, Germany;Univ Med Ctr Hamburg Eppendorf, Dept Stem Cell Transplantat, Hamburg, Germany
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- Vaid, Roshan (author)
- Uppsala universitet,Stockholms universitet,Institutionen för molekylär biovetenskap, Wenner-Grens institut,Uppsala University, Sweden,Institutionen för cell- och molekylärbiologi,Stockholm Univ, Wenner Gren Inst, Dept Mol Biosci, Stockholm, Sweden
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- Edelbroek, Bart (author)
- Uppsala universitet,Mikrobiologi
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- Li, Zhiru (author)
- Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA;New England Biolabs Inc, Ipswich, MA USA
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- Hoeppner, Marc P. (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi,Univ Kiel, Univ Hosp Schleswig Holstein, Inst Clin Mol Biol, Kiel, Germany
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- Grabherr, Manfred (author)
- Uppsala universitet,Institutionen för medicinsk biokemi och mikrobiologi
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- Isberg, Ralph R. (author)
- Tufts Univ, Sch Med, Dept Mol Biol & Microbiol, Boston, MA 02111 USA
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- Hagedorn, Monica (author)
- Bernhard Nocht Inst Trop Med, Sect Parasitol, Hamburg, Germany;Jacobs Univ Bremen gGmbH, Grp Ribogenet, Life Sci & Chem, Bremen, Germany
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- Söderbom, Fredrik (author)
- Uppsala universitet,Mikrobiologi
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(creator_code:org_t)
- 2019-12-10
- 2019
- English.
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In: BMC Genomics. - : Springer Science and Business Media LLC. - 1471-2164. ; 20:1
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Abstract
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- 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.
Subject headings
- NATURVETENSKAP -- Biologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Mikrobiologi inom det medicinska området (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Microbiology in the medical area (hsv//eng)
- NATURVETENSKAP -- Biologi -- Mikrobiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Microbiology (hsv//eng)
Keyword
- Host-pathogen
- Infection
- High-throughput sequencing
- Mycobacteria
- Legionella
- Dictyostelium discoideum
- Macrophage
- Infection model
- Pathogenic bacteria
- Intracellular pathogen
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Kjellin, Jonas
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Pränting, Maria
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Bach, Frauke
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Vaid, Roshan
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Edelbroek, Bart
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Li, Zhiru
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show more...
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Hoeppner, Marc P ...
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Grabherr, Manfre ...
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Isberg, Ralph R.
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Hagedorn, Monica
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Söderbom, Fredri ...
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Microbiology in ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Microbiology
- Articles in the publication
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BMC Genomics
- By the university
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Stockholm University
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Uppsala University