Mitochondrial respiration restricts Listeria monocytogenes infection by slowing down host cell receptor recycling
| Autor: | Spier, Anna, Connor, Michael, Steiner, Thomas, Carvalho, Filipe, Cossart, Pascale, Eisenreich, Wolfgang, Wai, Timothy, Stavru, Fabrizia |
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| Přispěvatelé: | Biologie Évolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, Université Paris Cité (UPCité)-Microbiologie Intégrative et Moléculaire (UMR6047), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Interactions Bactéries-Cellules, Institut Pasteur [Paris] (IP), Chromatine et Infection - Chromatin and Infection, Institut Pasteur [Paris] (IP)-Université Paris Cité (UPCité), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM), Université Paris Cité (UPCité), Biologie mitochondriale – Mitochondrial biology, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), This study was supported by the European Research Council ( H2020-ERC-2014-ADG 670823-BacCellEpi to P.C.), the DFG ( Project-ID EI 384/16-1 to W.E.), Institut Pasteur , and the Centre National de la Recherche Scientifique (CNRS). A.S. was supported by a BioSPC doctoral fellowship from the Université de Paris . M.G.C. is funded by a Pasteur Foundation Fellowship and his work was funded by ANR JCJC grant 'Epibactin.', We dedicate this work to the memory of Fabrizia Stavru. We thank Frédéric Bouillaud, Anne Lombès, and Nathalie Sauvonnet for useful advice, discussions, and support with Seahorse and endocytosis assays, Nam Tham for technical support, Werner Goebel for insightful discussions, Pierre-Henri Commere and members of the Cytometry & Biomarkers facility (CB_UTechS) at Institut Pasteur for training and help with flow cytometry and the Seahorse analyzer, and Alessandro Pagliuso and Simonetta Gribaldo for critical reading of the manuscript. Other bacterial species were GFP-expressing Salmonella enterica serovar Typhimurium strain 12023 (BUG2562) (a gift from Stéphane Méresse, Centre d’Immunologie de Marseille-Luminy, France) and Shigella flexneri M09T (BUG 2505) (a gift from Phillipe Sansonetti,Unité de Pathogénie Microbienne Moléculaire, Institut Pasteur, Paris). We thank Dr. Matthew Lawrenz at the University of Louisville for sharing the Rab11bCA construct generated by M.G.C. while in his laboratory., ANR-17-CE12-0007,EpiBactIn,Modifications epigenomiques induites par l'interaction hote-bacteries(2017), European Project: 670823,H2020,ERC-2014-ADG,BacCellEpi(2015), Biologie Evolutive de la Cellule Microbienne - Evolutionary Biology of the Microbial Cell, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris], Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Rok vydání: | 2021 |
| Předmět: |
[SDV]Life Sciences [q-bio]
Respiration Membrane Proteins Proto-Oncogene Proteins c-met HCT116 Cells Listeria monocytogenes infection Mitochondria endocytic recycling Mitochondrial Proteins mitochondrial disease 13C isotopologue profiling Report Rab11 Colonic Neoplasms Humans Listeriosis Energy Metabolism metabolism ComputingMilieux_MISCELLANEOUS |
| Zdroj: | Cell Reports Cell Reports, 2021, 37 (6), pp.109989. ⟨10.1016/j.celrep.2021.109989⟩ Cell Reports, Elsevier Inc, 2021, 37 (6), pp.109989. ⟨10.1016/j.celrep.2021.109989⟩ |
| ISSN: | 2211-1247 |
| Popis: | Summary Mutations in mitochondrial genes impairing energy production cause mitochondrial diseases (MDs), and clinical studies have shown that MD patients are prone to bacterial infections. However, the relationship between mitochondrial (dys)function and infection remains largely unexplored, especially in epithelial cells, the first barrier to many pathogens. Here, we generate an epithelial cell model for one of the most common mitochondrial diseases, Leigh syndrome, by deleting surfeit locus protein 1 (SURF1), an assembly factor for respiratory chain complex IV. We use this genetic model and a complementary, nutrient-based approach to modulate mitochondrial respiration rates and show that impaired mitochondrial respiration favors entry of the human pathogen Listeria monocytogenes, a well-established bacterial infection model. Reversely, enhanced mitochondrial energy metabolism decreases infection efficiency. We further demonstrate that endocytic recycling is reduced in mitochondrial respiration-dependent cells, dampening L. monocytogenes infection by slowing the recycling of its host cell receptor c-Met, highlighting a previously undescribed role of mitochondrial respiration during infection. Graphical abstract Highlights • Enhanced mitochondrial respiration decreases L. monocytogenes infection • Bacterial entry is affected by the host cell metabolism • Mitochondrial respiration restricts host cell receptor recycling and thus infection Spier et al. show that the cellular energy metabolism affects infection of epithelial cells by L. monocytogenes. Mitochondrial respiration modulates L. monocytogenes entry by limiting endocytic recycling of receptors such as c-Met back to the plasma membrane, leading to decreased bacterial load in cells with high respiratory activity. |
| Databáze: | OpenAIRE |
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