Aguilar, CarmenCosta, SusanaMaudet, ClaireVivek-Ananth, R.P.Zaldívar-López, SaraGarrido, Juan J.Samal, AreejitMano, MiguelEulalio, Ana2022-07-052022-07-052021-06-07Aguilar C, Costa S, Maudet C, Vivek-Ananth RP, Zaldívar-López S, Garrido JJ, et al. Reprogramming of microRNA expression via E2F1 downregulation promotes Salmonella infection both in infected and bystander cells. Nat Commun. 2021 Jun 7;12(1):3392http://hdl.handle.net/10668/3741Cells infected with pathogens can contribute to clearing infections by releasing signals that instruct neighbouring cells to mount a pro-inflammatory cytokine response, or by other mechanisms that reduce bystander cells' susceptibility to infection. Here, we show the opposite effect: epithelial cells infected with Salmonella Typhimurium secrete host factors that facilitate the infection of bystander cells. We find that the endoplasmic reticulum stress response is activated in both infected and bystander cells, and this leads to activation of JNK pathway, downregulation of transcription factor E2F1, and consequent reprogramming of microRNA expression in a time-dependent manner. These changes are not elicited by infection with other bacterial pathogens, such as Shigella flexneri or Listeria monocytogenes. Remarkably, the protein HMGB1 present in the secretome of Salmonella-infected cells is responsible for the activation of the IRE1 branch of the endoplasmic reticulum stress response in non-infected, neighbouring cells. Furthermore, E2F1 downregulation and the associated microRNA alterations promote Salmonella replication within infected cells and prime bystander cells for more efficient infection.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/Bacterial pathogenesisCellular microbiologyPathogensMiRNAsSalmonella InfectionsSalmonellaPatógenosMicroARNsInfecciones por SalmonellaMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Communication::Bystander EffectMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Down-RegulationMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Peptides::Intracellular Signaling Peptides and Proteins::Adaptor Proteins, Signal Transducing::Retinoblastoma Binding Proteins::E2F1 Transcription FactorMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Endoplasmic Reticulum StressMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Hydrolases::Esterases::Endonucleases::EndoribonucleasesMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::HeLa CellsMedical Subject Headings::Organisms::Bacteria::Gram-Positive Bacteria::Bacillales::Listeria::Listeria monocytogenesMedical Subject Headings::Phenomena and Processes::Chemical Phenomena::Biochemical Phenomena::Biochemical Processes::Signal Transduction::MAP Kinase Signaling SystemMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Protein Kinases::Protein-Serine-Threonine KinasesMedical Subject Headings::Diseases::Bacterial Infections and Mycoses::Bacterial Infections::Gram-Negative Bacterial Infections::Enterobacteriaceae Infections::Salmonella InfectionsMedical Subject Headings::Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Salmonella::Salmonella enterica::Salmonella typhimuriumMedical Subject Headings::Organisms::Bacteria::Gram-Negative Bacteria::Gram-Negative Facultatively Anaerobic Rods::Enterobacteriaceae::Shigella::Shigella flexneriresearch article34099666Acceso abierto10.1038/s41467-021-23593-z2041-1723PMC8184997