ArticleScientific reports2016
Role of Cathepsins in Mycobacterium tuberculosis Survival in Human Macrophages.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 102 citations in OpenAlex.
- Acne: epidemiology, risk factors, pathogenesis, management and cutting-edge research.Signal transduction and targeted therapy · 2026Review
- Genetic interference of distinctive Mycobacterium tuberculosis peptidoglycan modifications enhances β-lactam susceptibility and reveals expression-sensitive host immune dynamics.Scientific reports · 2026Article
- Faecal Cathepsin B and S Are Associated With Liver Disease Severity and Adiposity in MASLD.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- CD64-Targeted Polymer-Drug Conjugates Exploit Cathepsin K-Dependent Payload Release for Selective Elimination of Immunosuppressive Macrophages.Molecular pharmaceutics · 2026Article
- Cysteine Reactivity Profiling Identifies Host Regulators ofACS infectious diseases · 2026Article
- CST7Translational cancer research · 2025Article
- The pH-Dependent Specificity of Cathepsin S and Its Implications for Inflammatory Communications and Disease.Biochemistry · 2025Article
- Cysteine reactivity profiling identifies host regulators ofbioRxiv : the preprint server for biology · 2025Article
- Cathepsin Z is a conserved susceptibility factor underlying tuberculosis severity.PLoS biology · 2025Article
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- ACOD1-mediated lysosomal membrane permeabilization contributes toProceedings of the National Academy of Sciences of the United States of America · 2025Article
- The multifaceted roles of cathepsins in immune and inflammatory responses: implications for cancer therapy, autoimmune diseases, and infectious diseases.Biomarker research · 2024Review
- Cystatin F Depletion inInternational journal of molecular sciences · 2024Article
- Review
- Mycobacterium tuberculosis resides in lysosome-poor monocyte-derived lung cells during chronic infection.PLoS pathogens · 2024Article
- Proteomic analysis of granulomas from cattle and pigs naturally infected withFrontiers in immunology · 2024Article
- VapC12 ribonuclease toxin modulates host immune response duringFrontiers in immunology · 2024Article
- Mycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells.PloS one · 2024Article
- Modulation of Cystatin F in Human Macrophages Impacts Cathepsin-Driven Killing of Multidrug-ResistantMicroorganisms · 2023Article
- GRaNIE and GRaNPA: inference and evaluation of enhancer-mediated gene regulatory networks.Molecular systems biology · 2023Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cathepsins are proteolytic enzymes that function in the endocytic pathway, especially in lysosomes, where they contribute directly to pathogen killing or indirectly, by their involvement in the antigen presentation pathways. Mycobacterium tuberculosis (MTB) is a facultative intracellular pathogen that survives inside the macrophage phagosomes by inhibiting their maturation to phagolysosomes and thus avoiding a low pH and protease-rich environment. We previously showed that mycobacterial inhibition of the proinflammatory transcription factor NF-κB results in impaired delivery of lysosomal enzymes to phagosomes and reduced pathogen killing. Here, we elucidate how MTB also controls cathepsins and their inhibitors, cystatins, at the level of gene expression and proteolytic activity. MTB induced a general down-regulation of cathepsin expression in infected cells, and inhibited IFNγ-mediated increase of cathepsin mRNA. We further show that a decrease in cathepsins B, S and L favours bacterial survival within human primary macrophages. A siRNA knockdown screen of a large set of cathepsins revealed that almost half of these enzymes have a role in pathogen killing, while only cathepsin F coincided with MTB resilience. Overall, we show that cathepsins are important for the control of MTB infection, and as a response, it manipulates their expression and activity to favour its intracellular survival.
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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.