ArticleCommunications biology2022
Mycobacterium tuberculosis senses host Interferon-γ via the membrane protein MmpL10.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 20 citations in OpenAlex.
- A Clinical Multicenter Trial of Recombinant Human Interferon Gamma in Tuberculosis (GAM2022): Experience with the Use of Human Recombinant Interferon Gamma in TB Practice.Infectious disorders drug targets · 2025Trial
- Comparative proteomics reveals distinct functions and localization of invasive Entamoeba histolytica and non-invasive Entamoeba moshkovskii proteins.Parasites & vectors · 2026Article
- Dynamics of IFN-γ, IL-2, and IL-6 during early tuberculosis treatment: significant longitudinal changes but limited value as standalone discriminators of treatment status.BMC microbiology · 2026Article
- Evolution of the tuberculin skin test reveals generalisable Mtb-reactive T cell metaclones.Nature communications · 2026Article
- Drug resistance mechanisms inFrontiers in pharmacology · 2026Review
- Lineage-Dependent IFN-γ Responses to Drug-Sensitive and Isoniazid-ResistantInfection and drug resistance · 2026Article
- Natural and synthetic chemicals acting as enhancers of bacterial pathogenic success within the human host.Frontiers in cellular and infection microbiology · 2026Review
- Mycobacterium tuberculosis biology, pathogenicity and interaction with the host.Nature reviews. Microbiology · 2025Review
- Interferon-γ Stimulation Fails to Restrict Mycobacterium tuberculosis Growth in Human Monocyte-Derived and Alveolar Macrophages.The Journal of infectious diseases · 2025Article
- Molecules-mediated bidirectional interactions between microbes and human cells.NPJ biofilms and microbiomes · 2025Review
- Microbial adaptive pathogenicity strategies to the host inflammatory environment.FEMS microbiology reviews · 2025Review
- rBCG-LTAK63 enhances protection against tuberculosis by inducing autophagy and circadian gene regulation.Frontiers in immunology · 2025Article
- Atomic-level binding interaction analysis ofIn silico pharmacology · 2025Article
- Enhancement of mycobacterial pathogenesis by host interferon-γ.Cellular and molecular life sciences : CMLS · 2024Article
- Mycobacterium tuberculosis strain with deletions in menT3 and menT4 is attenuated and confers protection in mice and guinea pigs.Nature communications · 2024Article
- Impact of MSMEG5257 Deletion onMicroorganisms · 2024Article
- Monitoring host-pathogen interactions using chemical proteomics.RSC chemical biology · 2024Review
- Latent Tuberculosis Patients Have an Increased Frequency of IFN-γ-Producing CD5+ B Cells, Which Respond Efficiently to Mycobacterial Proteins.Pathogens (Basel, Switzerland) · 2023Article
- Cancer-biomarkers associated with sex hormone receptors and recent therapeutic advancements: a comprehensive review.Medical oncology (Northwood, London, England) · 2023Review
- Understanding the tuberculosis granuloma: the matrix revolutions.Trends in molecular medicine · 2022Review
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 3 countries.
Funding
Abstract
Mycobacterium tuberculosis (Mtb) is one of the most successful human pathogens. Several cytokines are known to increase virulence of bacterial pathogens, leading us to investigate whether Interferon-γ (IFN-γ), a central regulator of the immune defense against Mtb, has a direct effect on the bacteria. We found that recombinant and T-cell derived IFN-γ rapidly induced a dose-dependent increase in the oxygen consumption rate (OCR) of Mtb, consistent with increased bacterial respiration. This was not observed in attenuated Bacillus Calmette-Guérin (BCG), and did not occur for other cytokines tested, including TNF-α. IFN-γ binds to the cell surface of intact Mtb, but not BCG. Mass spectrometry identified mycobacterial membrane protein large 10 (MmpL10) as the transmembrane binding partner of IFN-γ, supported by molecular modelling studies. IFN-γ binding and the OCR response was absent in Mtb Δmmpl10 strain and restored by complementation with wildtype mmpl10. RNA-sequencing and RT-PCR of Mtb exposed to IFN-γ revealed a distinct transcriptional profile, including genes involved in virulence. In a 3D granuloma model, IFN-γ promoted Mtb growth, which was lost in the Mtb Δmmpl10 strain and restored by complementation, supporting the involvement of MmpL10 in the response to IFN-γ. Finally, IFN-γ addition resulted in sterilization of Mtb cultures treated with isoniazid, indicating clearance of phenotypically resistant bacteria that persist in the presence of drug alone. Together our data are the first description of a mechanism allowing Mtb to respond to host immune activation that may be important in the immunopathogenesis of TB and have use in novel eradication strategies.
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Registered trials
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