ArticleNature microbiology2020
Spatiotemporal proteomics uncovers cathepsin-dependent macrophage cell death during Salmonella infection.
Article in Nature microbiology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Opsonization Improves Dual Proteomic Analysis ofJournal of proteome research · 2026Article
- MAP4Ks drive cell death in response tomBio · 2026Article
- In Situ Synthesis of Covalent Organic Frameworks Inside Cells for Triggering Ferroptosis and Immunotherapy.Advanced materials (Deerfield Beach, Fla.) · 2026Article
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- Coxiella burnetii manipulates the lysosomal protease cathepsin B to facilitate intracellular success.Nature communications · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.Military Medical Research · 2024Review
- A host-directed oxadiazole compound potentiates antituberculosis treatment via zinc poisoning in human macrophages and in a mouse model of infection.PLoS biology · 2024Article
- A pathogen-specific isotope tracing approach reveals metabolic activities and fluxes of intracellular Salmonella.PLoS biology · 2023Article
- Visualisation of Host-Pathogen Communication.Advances in experimental medicine and biology · 2023Article
- Lysosomal damage drives mitochondrial proteome remodelling and reprograms macrophage immunometabolism.Nature communications · 2022Article
- Microscopy-based phenotypic profiling of infection by Staphylococcus aureus clinical isolates reveals intracellular lifestyle as a prevalent feature.Nature communications · 2022Article
- Proteomic characterization of phagocytic primary human monocyte-derived macrophages.RSC chemical biology · 2022Article
- Article
- Low-level lysosomal membrane permeabilization for limited release and sublethal functions of cathepsin proteases in the cytosol and nucleus.FEBS open bio · 2022Review
- Protein turnover in the developing Triticum aestivum grain.The New phytologist · 2022Article
- Spatial localization of cathepsins: Implications in immune activation and resolution during infections.Frontiers in immunology · 2022Review
- Proteomic Approaches to Unravel Mechanisms of Antibiotic Resistance and Immune Evasion of Bacterial Pathogens.Frontiers in medicine · 2022Review
- Activation of NLRP3 Inflammasome by Virus-Like Particles of Human Polyomaviruses in Macrophages.Frontiers in immunology · 2022Article
- Host metabolic shift during systemicEmerging microbes & infections · 2021Article
Corrections and comments
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Authors and funding
21 authors at 9 institutions in 7 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The interplay between host and pathogen relies heavily on rapid protein synthesis and accurate protein targeting to ensure pathogen destruction. To gain insight into this dynamic interface, we combined Click chemistry with pulsed stable isotope labelling of amino acids in cell culture to quantify the host proteome response during macrophage infection with the intracellular bacterial pathogen Salmonella enterica Typhimurium. We monitored newly synthesized proteins across different host cell compartments and infection stages. Within this rich resource, we detected aberrant trafficking of lysosomal proteases to the extracellular space and the nucleus. We verified that active cathepsins re-traffic to the nucleus and that these are linked to cell death. Pharmacological cathepsin inhibition and nuclear targeting of a cellular cathepsin inhibitor (stefin B) suppressed S. enterica Typhimurium-induced cell death. We demonstrate that cathepsin activity is required for pyroptotic cell death via the non-canonical inflammasome, and that lipopolysaccharide transfection into the host cytoplasm is sufficient to trigger active cathepsin accumulation in the host nucleus and cathepsin-dependent cell death. Finally, cathepsin inhibition reduced gasdermin D expression, thus revealing an unexpected role for cathepsin activity in non-canonical inflammasome regulation. Overall, our study illustrates how resolution of host proteome dynamics during infection can drive the discovery of biological mechanisms at the host-microbe interface.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.