IFN-γ-Driven macrophage responses in the immunity to Mycobacterium tuberculosis and Mycobacterium leprae

Interferon-gamma (IFN-γ) is a key stimulator of macrophage defense against Mycobacterium tuberculosis (Mtb) and Mycobacterium leprae (M. leprae). Both pathogens adopt measures to circumvent the effects of the immune system, weakening the impact of IFN-γ and enabling them to survive in the cells. This review synthesizes how IFN-γ overdose transacts the JAK/STAT1-IRF1-transmitter to encourage maturation of phagolysosomes, reactive oxygen and nitrogen product generation, LC3-associated phagocytosis (LAP), autophagy, and improved antigen presentation and juxtaposes these pathways in tuberculosis and leprosy. We also explain the mechanisms by which mycobacteria counter this axis, including receptor downregulation, induction of IL-10/SOCS, type I INF antagonism, and the impact of miRNA. Additionally, we assessed the translational application, emphasizing its benefits, potential risks, and sources of variability. Additionally, we discuss biomarker strategies related to IFN-γ activity, such as gene signatures associated with HIF-1 and active IFN-γ measurements, which could aid in selecting patients and tracking their treatment progress. The results show that macrophage-related processes are important for the treatment and diagnosis of TB and leprosy when they occur simultaneously. This highlights the need for safe and effective treatments that focus on the host and balance the protective and harmful effects of IFN-γ.

• Publication year

  2025

• Venue

  Frontiers in Cellular and Infection Microbiology

• Publication date

  2025-11-11

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.3389/fcimb.2025.1679691PMID 41306590PMCID 12644087
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Exploring the Neurological Manifestations of Leprosy: Clinical Insights and Implications

  2025cited by this paper
• Nutrient regulation targeting macrophage-controlled intestinal mucosal healing: A promising strategy against intestinal mucositis induced by deoxynivalenol.

  2025cited by this paper
• Isoorientin Ameliorates Macrophage Pyroptosis and Atherogenesis by Reducing KDM4A Levels and Promoting SKP1-Cullin1-F-box E3 Ligase-mediated NLRP3 Ubiquitination

  2025cited by this paper
• An update on leprosy immunopathogenesis: systematic review

  2024cited by this paper
• Cigarette Smoke Extract-Treated Mouse Airway Epithelial Cells-Derived Exosomal LncRNA MEG3 Promotes M1 Macrophage Polarization and Pyroptosis in Chronic Obstructive Pulmonary Disease by Upregulating TREM-1 via m6A Methylation

  2024cited by this paper
• Mycobacterium tuberculosis: immune response, biomarkers, and therapeutic intervention

  2024cited by this paper
• The role of ESAT-6 in tuberculosis immunopathology

  2024cited by this paper
• Intracellular peroxynitrite perturbs redox balance, bioenergetics, and Fe–S cluster homeostasis in Mycobacterium tuberculosis

  2024cited by this paper
• T cells in health and disease

  2023cited by this paper
• M1/M2 macrophages and their overlaps – myth or reality?

  2023cited by this paper
• Pathogenicity of Type I Interferons in Mycobacterium tuberculosis

  2023cited by this paper
• Mycobacterium tuberculosis-macrophage interaction: Molecular updates

  2023cited by this paper
• Challenges and advances in serological and molecular tests to aid leprosy diagnosis

  2023cited by this paper
• Interferons and Resistance Mechanisms in Tumors and Pathogen-Driven Diseases—Focus on the Major Histocompatibility Complex (MHC) Antigen Processing Pathway

  2023cited by this paper
• Immune evasion and provocation by Mycobacterium tuberculosis

  2022cited by this paper
• STAT1 and Its Crucial Role in the Control of Viral Infections

  2022cited by this paper
• Pathogenicity and virulence of Mycobacterium leprae

  2022cited by this paper
• MicroRNAs as immune regulators and biomarkers in tuberculosis

  2022cited by this paper
• CTLs: Killers of intracellular bacteria

  2022cited by this paper
• Reactive oxygen species function as signaling molecules in controlling plant development and hormonal responses.

  2022cited by this paper
• Case Report: A Case Series of Immunobiological Therapy (Anti-TNF-α) for Patients With Erythema Nodosum Leprosum

  2022cited by this paper
• Advancing Adjuvants for Mycobacterium tuberculosis Therapeutics

  2021cited by this paper
• IFN-γ-independent control of M. tuberculosis requires CD4 T cell-derived GM-CSF and activation of HIF-1α

  2021cited by this paper
• Macrophage-targeted nanomedicine for chronic diseases immunotherapy

  2021cited by this paper
• Host-Related Laboratory Parameters for Leprosy Reactions

  2021cited by this paper
• Regulation of Interferon-γ receptor (IFN-γR) expression in macrophages during Mycobacterium tuberculosis infection

  2020cited by this paper
• Emerging Evasion Mechanisms of Macrophage Defenses by Pathogenic Bacteria

  2020cited by this paper
• The immunology of other mycobacteria: M. ulcerans, M. leprae

  2020cited by this paper
• Biologics in Leprosy: A Systematic Review and Case Report.

  2020cited by this paper
• Multi-parameter flow cytometry immunophenotyping distinguishes different stages of tuberculosis infection.

  2020cited by this paper
• Immune Response to Mycobacterium tuberculosis: A Narrative Review

  2019cited by this paper
• Transcription factors STAT-4, STAT-6 and CREB regulate Th1/Th2 response in leprosy patients: effect of M. leprae antigens

  2019cited by this paper
• Mycobacterium tuberculosis infection of host cells in space and time

  2019cited by this paper
• Intracellular Pathogens: Host Immunity and Microbial Persistence Strategies

  2019cited by this paper
• The Immune Escape Mechanisms of Mycobacterium Tuberculosis

  2019cited by this paper
• Positive association between MIC gene polymorphism and tuberculosis in Chinese population.

  2019cited by this paper
• Intrinsic activation of the vitamin D antimicrobial pathway by M. leprae infection is inhibited by type I IFN

  2018cited by this paper
• Mycobacterium tuberculosis WhiB3 maintains redox homeostasis and survival in response to reactive oxygen and nitrogen species

  2018cited by this paper
• Vitamin D: Nutrient, Hormone, and Immunomodulator

  2018cited by this paper
• IFN-γ immune priming of macrophages in vivo induces prolonged STAT1 binding and protection against Cryptococcus neoformans

  2018cited by this paper
• Chemical and genetic control of IFNγ‐induced MHCII expression

  2018cited by this paper
• Correlates of immune exacerbations in leprosy.

  2018cited by this paper
• Interferon-gamma (IFN-γ): Exploring its implications in infectious diseases

  2018cited by this paper
• Vaccines for Leprosy and Tuberculosis: Opportunities for Shared Research, Development, and Application

  2018cited by this paper
• CD4+ AND CD8+ T-CELLS EXPRESSING INTERFERON GAMMA IN ACTIVE PULMONARY TUBERCULOSIS PATIENTS

  2018cited by this paper
• Emerging Concepts of Adaptive Immunity in Leprosy

  2018cited by this paper
• Longitudinal assessment of anti-PGL-I serology in contacts of leprosy patients in Bangladesh

  2017cited by this paper
• MicroRNA-155 induction via TNF-α and IFN-γ suppresses expression of programmed death ligand-1 (PD-L1) in human primary cells

  2017cited by this paper
• The influence of innate and adaptative immune responses on the differential clinical outcomes of leprosy

  2017cited by this paper
• Leprosy As a Complex Infection: Breakdown of the Th1 and Th2 Immune Paradigm in the Immunopathogenesis of the Disease

  2017cited by this paper
• Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy

  2017cited by this paper
• Th1 cytokines, true functional signatures for protective immunity against TB?

  2017cited by this paper
• IFN-γ extends the immune functions of Guanylate Binding Proteins to inflammasome-independent antibacterial activities during Francisella novicida infection

  2017cited by this paper
• Expression of gp91phox and p22phox, catalytic subunits of NADPH oxidase, on microglia in Nasu-Hakola disease brains.

  2016cited by this paper
• Heat shock proteins (HSPs) in the homeostasis of regulatory T cells (Tregs)

  2016cited by this paper
• LAP-like process as an immune mechanism downstream of IFN-γ in control of the human malaria Plasmodium vivax liver stage

  2016cited by this paper
• S100A12 Is Part of the Antimicrobial Network against Mycobacterium leprae in Human Macrophages

  2016cited by this paper
• Mycobacterium leprae-induced Insulin-like Growth Factor I attenuates antimicrobial mechanisms, promoting bacterial survival in macrophages

  2016cited by this paper
• Mycobacterium leprae alters classical activation of human monocytes in vitro

  2016cited by this paper
• Interferon-Gamma Improves Macrophages Function against M. tuberculosis in Multidrug-Resistant Tuberculosis Patients

  2016cited by this paper
• Type I IFN Inhibits Alternative Macrophage Activation during Mycobacterium tuberculosis Infection and Leads to Enhanced Protection in the Absence of IFN-γ Signaling

  2016cited by this paper
• HIF-1α Is an Essential Mediator of IFN-γ–Dependent Immunity to Mycobacterium tuberculosis

  2016cited by this paper
• The Reactive Oxygen Species in Macrophage Polarization: Reflecting Its Dual Role in Progression and Treatment of Human Diseases

  2016cited by this paper
• Latent Mycobacterium tuberculosis Infection and Interferon-Gamma Release Assays

  2016cited by this paper
• Autophagy in the Fight Against Tuberculosis

  2015cited by this paper
• Mycobacterium tuberculosis metabolism.

  2015cited by this paper
• Mycobacterium tuberculosis Decreases Human Macrophage IFN-γ Responsiveness through miR-132 and miR-26a

  2014cited by this paper
• Protection against Mycobacterium leprae Infection by the ID83/GLA-SE and ID93/GLA-SE Vaccines Developed for Tuberculosis

  2014cited by this paper
• Immunoregulation of host macrophage responses by Mycobacterium tuberculosis

  2014cited by this paper
• rBCG30-Induced Immunity and Cross-Protection against Mycobacterium leprae Challenge Are Enhanced by Boosting with the Mycobacterium tuberculosis 30-Kilodalton Antigen 85B

  2014cited by this paper
• Mycobacterium leprae intracellular survival relies on cholesterol accumulation in infected macrophages: a potential target for new drugs for leprosy treatment

  2014cited by this paper
• Drug Resistance Mechanisms in Mycobacterium tuberculosis

  2014cited by this paper
• Type I IFN signaling triggers immunopathology in tuberculosis-susceptible mice by modulating lung phagocyte dynamics

  2014cited by this paper
• Metabolism via Arginase or Nitric Oxide Synthase: Two Competing Arginine Pathways in Macrophages

  2014cited by this paper
• CD4+ T‐cell depletion in HIV infection: mechanisms of immunological failure

  2013cited by this paper
• Evolution of the Macrophage CD163 Phenotype and Cytokine Profiles in a Human Model of Resolving Inflammation

  2013cited by this paper
• Observation of autophagosome maturation in the interferon-γ-primed and lipopolysaccharide-activated macrophages using a tandem fluorescent tagged LC3.

  2013cited by this paper
• Effect of Malnutrition on the Expression of Cytokines Involved in Th1 Cell Differentiation

  2013cited by this paper
• An in vitro model of Mycobacterium leprae induced granuloma formation

  2013cited by this paper
• The armadillo: a model for the neuropathy of leprosy and potentially other neurodegenerative diseases

  2012cited by this paper
• Interferon-γ induces autophagy with growth inhibition and cell death in human hepatocellular carcinoma (HCC) cells through interferon-regulatory factor-1 (IRF-1).

  2012cited by this paper
• Role of TNF-Alpha, IFN-Gamma, and IL-10 in the Development of Pulmonary Tuberculosis

  2012cited by this paper
• Sustained generation of nitric oxide and control of mycobacterial infection requires argininosuccinate synthase 1.

  2012cited by this paper
• IL-6 inhibits IFN-γ induced autophagy in Mycobacterium tuberculosis H37Rv infected macrophages.

  2012cited by this paper
• Adjunctive therapy with interferon-gamma for the treatment of pulmonary tuberculosis: a systematic review.

  2011cited by this paper
• Vitamin D Is Required for IFN-γ–Mediated Antimicrobial Activity of Human Macrophages

  2011cited by this paper
• Activated STAT1 transcription factors conduct distinct saltatory movements in the cell nucleus.

  2011cited by this paper
• Role of innate cytokines in mycobacterial infection

  2011cited by this paper
• The immunology of tuberculosis: From bench to bedside

  2010cited by this paper
• IL-17 and Th17 cells in tuberculosis.

  2010cited by this paper
• Interferon-γ Regulates the Death of M. tuberculosis-Infected Macrophages

  2010cited by this paper
• GM-CSF-mediated T-cell activation by macrophages infected with recombinant BCG that secretes major membrane protein-II of Mycobacterium leprae.

  2009cited by this paper
• Divergence of macrophage phagocytic and antimicrobial programs in leprosy.

  2009cited by this paper
• A new recombinant bacille Calmette-Guérin vaccine safely induces significantly enhanced tuberculosis-specific immunity in human volunteers.

  2008cited by this paper
• Expression and characterization of recombinant interferon gamma (IFN-gamma) from the nine-banded armadillo (Dasypus novemcinctus) and its effect on Mycobacterium leprae-infected macrophages.

  2008cited by this paper
• Mycobacterium tuberculosis and the macrophage: maintaining a balance.

  2008cited by this paper
• Modulation of the Phagosome Proteome by Interferon-γ*S

  2008cited by this paper
• Activation of the JAK/STAT-1 Signaling Pathway by IFN-γ Can Down-Regulate Functional Expression of the MHC Class I-Related Neonatal Fc Receptor for IgG1

  2008cited by this paper
• Mycobacterium tuberculosis-Specific CD8+ T Cells Require Perforin to Kill Target Cells and Provide Protection In Vivo1

  2008cited by this paper
• Macrophage receptors implicated in the "adaptive" form of innate immunity.

  2007cited by this paper

• No citing papers are available for this paper.