ArticleCell death & disease2014
Mycobacterium tuberculosis ESAT-6 is a leukocidin causing Ca2+ influx, necrosis and neutrophil extracellular trap formation.
Article in Cell death & disease, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 92 citations in OpenAlex.
- NETosis associates with human TB lung tissue destruction and disease pathogenesis.EMBO molecular medicine · 2026Article
- Cell death crosstalk in NET-Driven inflammation: mechanisms, disease contexts, and therapeutic perspectives.Biomarker research · 2026Review
- Mycobacterium tuberculosis biology, pathogenicity and interaction with the host.Nature reviews. Microbiology · 2025Review
- Immunoregulation by ESAT-6: From Pathogenesis of Tuberculosis to Potential Anti-Inflammatory and Anti-Rejection Application.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Machine learning-driven discovery of NETs-associated diagnostic biomarkers and molecular subtypes in tuberculosis.Frontiers in cellular and infection microbiology · 2025Article
- Optimizing antigen selection for the development of tuberculosis vaccines.Cell insight · 2024Review
- The role of ESAT-6 in tuberculosis immunopathology.Frontiers in immunology · 2024Review
- A Putative Role for TRPC6 in Immune-Mediated Kidney Injury.International journal of molecular sciences · 2023Review
- Review
- Virulence Factors ofPathogens (Basel, Switzerland) · 2023Review
- Neutrophils inVaccines · 2023Review
- Article
- Role of phagocyte extracellular traps duringFrontiers in microbiology · 2023Review
- TWEAK-Fn14 Axis Induces Calcium-Associated Autophagy and Cell Death To Control Mycobacterial Survival in Macrophages.Microbiology spectrum · 2022Article
- Different modalities of host cell death and their impact onAmerican journal of physiology. Cell physiology · 2022Review
- Article
- It Takes a Village: The Multifaceted Immune Response toFrontiers in immunology · 2022Review
- Article
- Whole transcriptome sequencing reveals neutrophils' transcriptional landscape associated with active tuberculosis.Frontiers in immunology · 2022Article
- Role of Extracellular Trap Release During Bacterial and Viral Infection.Frontiers in microbiology · 2022Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mycobacterium tuberculosis infection generates pulmonary granulomas that consist of a caseous, necrotic core surrounded by an ordered arrangement of macrophages, neutrophils and T cells. This inflammatory pathology is essential for disease transmission and M. tuberculosis has evolved to stimulate inflammatory granuloma development while simultaneously avoiding destruction by the attracted phagocytes. The most abundant phagocyte in active necrotic granulomas is the neutrophil. Here we show that the ESAT-6 protein secreted by the ESX-1 type VII secretion system causes necrosis of the neutrophils. ESAT-6 induced an intracellular Ca(2+) overload followed by necrosis of phosphatidylserine externalised neutrophils. This necrosis was dependent upon the Ca(2+) activated protease calpain, as pharmacologic inhibition prevented this secondary necrosis. We also observed that the ESAT-6 induced increase in intracellular Ca(2+), stimulated the production of neutrophil extracellular traps characterised by extruded DNA and myeloperoxidase. Thus we conclude that ESAT-6 has a leukocidin function, which may facilitate bacterial avoidance of the antimicrobial action of the neutrophil while contributing to the maintenance of inflammation and necrotic pathology necessary for granuloma formation and TB transmission.
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