ArticleThe EMBO journal2023
Uptake-independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates.
Article in The EMBO journal, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 33 citations in OpenAlex.
- Article
- Article
- Functional analysis of type VII secretion system links to host immune evasion mechanism inFrontiers in cellular and infection microbiology · 2026Review
- Control of Mycobacterium tuberculosis protein secretion by ESX-4 and the outer membrane EsxUT-EsxEF complex.Nature communications · 2025Article
- Article
- The Regulatory Mechanisms of Treponema pallidum Enolase on Macrophages: From Enzymatic Activity to Signal Transduction.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- A glycosylated lipooctapeptide promotes uptake and growth of Mycobacterium abscessus in the host.Nature communications · 2025Article
- Zinc-limitedInfection and immunity · 2025Article
- Metagenomic Analysis of Caseum of Tuberculosis Foci.Bulletin of experimental biology and medicine · 2025Article
- 3D Hydrogel Culture System Recapitulates Key Tuberculosis Phenotypes and Demonstrates Pyrazinamide Efficacy.Advanced healthcare materials · 2025Article
- Dynamic interplay of autophagy and membrane repair during Mycobacterium tuberculosis Infection.PLoS pathogens · 2025Article
- Type I interferon exacerbates Mycobacterium tuberculosis induced human macrophage death.EMBO reports · 2024Article
- Exploring host-pathogen interactions in the Dictyostelium discoideum-Mycobacterium marinum infection model of tuberculosis.Disease models & mechanisms · 2024Review
- circRNA_SLC8A1 promotes the survival of mycobacterium tuberculosis in macrophages by upregulating expression of autophagy-related protein SQSTM1/p62 to activate the NF-κB pathway.Scientific reports · 2024Article
- Understanding bacterial pathogenicity: a closer look at the journey of harmful microbes.Frontiers in microbiology · 2024Review
- Identification and Validation of Genes Related to Macrophage Polarization and Cell Death Modes UnderJournal of inflammation research · 2024Article
- Antibodies as key mediators of protection againstFrontiers in immunology · 2024Review
- Article
- Bifurcation analysis of a tuberculosis progression model for drug target identification.Scientific reports · 2023Article
- Uptake-independent killing of macrophages by extracellular Mycobacterium tuberculosis aggregates.The EMBO journal · 2023Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacterium tuberculosis (Mtb) infection is initiated by inhalation of bacteria into lung alveoli, where they are phagocytosed by resident macrophages. Intracellular Mtb replication induces the death of the infected macrophages and the release of bacterial aggregates. Here, we show that these aggregates can evade phagocytosis by killing macrophages in a contact-dependent but uptake-independent manner. We use time-lapse fluorescence microscopy to show that contact with extracellular Mtb aggregates triggers macrophage plasma membrane perturbation, cytosolic calcium accumulation, and pyroptotic cell death. These effects depend on the Mtb ESX-1 secretion system, however, this system alone cannot induce calcium accumulation and macrophage death in the absence of the Mtb surface-exposed lipid phthiocerol dimycocerosate. Unexpectedly, we found that blocking ESX-1-mediated secretion of the EsxA/EsxB virulence factors does not eliminate the uptake-independent killing of macrophages and that the 50-kDa isoform of the ESX-1-secreted protein EspB can mediate killing in the absence of EsxA/EsxB secretion. Treatment with an ESX-1 inhibitor reduces uptake-independent killing of macrophages by Mtb aggregates, suggesting that novel therapies targeting this anti-phagocytic mechanism could prevent the propagation of extracellular bacteria within the lung.
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Registered trials
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.