Specific immune response to M. tuberculosis and ability to in vitro control mycobacterial replication are not impaired in subjects with immune-mediated inflammatory disease and tuberculosis infection

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 13, 2025

Background Subjects with immune-mediated inflammatory diseases (IMID), such as rheumatoid arthritis, tuberculosis infection (TBI), have a high probability of progressing to disease (TB). We aim characterize the impact IMID on immune response M. (Mtb) in patients TBI and TB disease. Methods enrolled without IMID. Peripheral blood mononuclear cells (PBMCs) were stimulated Mtb-derived epitopes (MTB300). By flow-cytometry, we identified Mtb-specific CD4 + T cytokine-producing or CD25 CD134 cells. Memory activation status assessed by evaluating: CD153, HLA-DR, CD45RA, CD27. Mycobacterial growth inhibition assay (MGIA) was used evaluate ability PBMCs inhibit mycobacteria growth. A long-term stimulation detect memory response. Results The therapy did not affect magnitude Mtb-antigen number responders. TBI-IMID showed cytokine profile like patients. Mtb characterized an effector central phenotype groups. This allowed increased IFN-γ production after 6 days MTB300-stimulation. HLA-DR expression associated TB, whereas CD153 status. Finally, had MGIA Conclusion condition does key aspects Mtb, response, profile, contain replication. immunological characterization fragile population is fundamental understanding correlation between protection

Language: Английский

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Necrosis drives susceptibility to Mycobacterium tuberculosis in Polg ^D257A mutator mice

Infection and Immunity, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 19, 2025

ABSTRACT The genetic and molecular determinants that underlie the heterogeneity of Mycobacterium tuberculosis (Mtb) infection outcomes in humans are poorly understood. Multiple lines evidence demonstrate mitochondrial dysfunction can exacerbate mycobacterial disease severity, mutations some genes confer susceptibility to humans. Here, we report mitochondria DNA (mtDNA) polymerase gamma potentiate Mtb mice. Polg D257A mutator mtDNA mice fail mount a protective innate immune response at an early time point, evidenced by high bacterial burdens, reduced M1 macrophages, excessive neutrophil infiltration lungs. Immunohistochemistry reveals signs enhanced necrosis lungs Mtb-infected mice, macrophages hypersusceptible extrinsic triggers necroptosis ex vivo . By assigning role for driving during infection, this work further highlights requirement homeostasis mounting balanced responses Mtb.

Language: Английский

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Tuberculosis Vaccines and T Cell Immune Memory

Vaccines, Journal Year: 2024, Volume and Issue: 12(5), P. 483 - 483

Published: April 30, 2024

Tuberculosis (TB) remains a major infectious disease partly due to the lack of an effective vaccine. Therefore, developing new and more TB vaccines is crucial for controlling TB.

Language: Английский

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Mechanism- and data-driven algorithms of electrical energy consumption accounting and prediction for medium and heavy plate rolling

Mathematical Biosciences & Engineering, Journal Year: 2025, Volume and Issue: 22(3), P. 511 - 527

Published: Jan. 1, 2025

Tuberculosis is the leading cause of death worldwide from a single infectious agent; it has also been declared threat to humanity by World Health Organization. New insights indicate that innate immune response plays crucial role in determining outcome infection. In this study, we assessed macrophages through simple mathematical model. Our results confirm provide primary protective against Mycobacterium tuberculosis. However, they highlight importance other cells Specifically, our findings suggest that, addition macrophage activity, involvement essential for eliminating or controlling bacterial progression, ultimately an adaptive response.

Language: Английский

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Stem cell-based therapies and organoid models: Advancing tuberculosis treatment and research

Deleted Journal, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 12

Published: March 20, 2025

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), remains a global health challenge despite advances in conventional treatments. The limitations of traditional anti-tuberculosis therapies, such as prolonged treatment duration, drug resistance, and tissue damage, necessitate innovative approaches. Stem cell-based therapies have emerged promising avenue due to their immunomodulatory, regenerative, drug-delivery capabilities. This review discussed the pathogenesis potential various stem cell types, including mesenchymal cells (MSCs), hematopoietic (HSCs), induced pluripotent (iPSCs), management. It delved into mechanisms, immune regulation, repair, targeted delivery. Additionally, this summarized application cell-derived organoid technology establishing vitro models. These organoids, three-dimensional structures derived from cells, mimic architecture function organs like lungs, providing platform study Mtb infection dynamics, host-pathogen interactions, screening. Altogether, therapy, complemented organoid-based models, offers transformative for advancing research, particularly drug-resistant immunocompromised patients.

Language: Английский

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Serine protease Rv2569c inhibits inflammatory response and promotes intracellular survival of Mycobacterium tuberculosis by targeting the RhoG-NF-κB-NLRP3 pathway

International Journal of Biological Macromolecules, Journal Year: 2025, Volume and Issue: 309, P. 143022 - 143022

Published: April 12, 2025

Language: Английский

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Turning the Tables: Loss of Adaptive Immunity Reverses Sex Differences in Tuberculosis

Immuno, Journal Year: 2025, Volume and Issue: 5(1), P. 4 - 4

Published: Jan. 4, 2025

Sex-based differences in innate immunity may play a crucial role susceptibility to and progression of tuberculosis (TB), disease that disproportionately affects men. This study aimed examine whether early host–pathogen interactions contribute the heightened vulnerability males Mycobacterium (Mtb) infection. Using recombination activating gene 2 knockout (RAG2 KO) mice, which lack adaptive immunity, we were able isolate analyze immune responses Mtb without influence T B cells. Surprisingly, stark contrast wild-type mice reflect male bias as observed humans, female RAG2 KO more susceptible than their counterparts. Increased lung CFU females was accompanied by significant rise inflammation, indicated elevated levels inflammatory cytokines chemokines, well massive influx neutrophils into lungs. In contrast, exhibited higher IFN-γ CCL5, along with greater presence NK cells lungs, suggesting that, absence benefit from robust cell response, potentially offering protection better controlling inflammation slowing progression.

Language: Английский

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Isoniazid and nicotinic hydrazide hybrids mitigate trehalose-6,6’-dimycolate-induced inflammatory responses and pulmonary granulomas via Syk/PI3K pathways: A promising host-directed therapy for tuberculosis

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 183, P. 117798 - 117798

Published: Jan. 6, 2025

Language: Английский

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Systematic review of innate immune responses against Mycobacterium tuberculosis complex infection in animal models

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 30, 2025

Background Mycobacterium tuberculosis (Mtb) complex (MTBC) includes ten species that affect mammals and pose a significant global health concern. Upon infection, Mtb induces various stages in the host, including early bacterial elimination, which may or not involve memory responses. Deciphering role of innate immune responses during MTBC infection is crucial for understanding disease progression protection. Over past decade, there has been growing interest response to , with new preclinical models emerging. Methods We conducted systematic review following PRISMA guidelines, focused on mediators linked protection animal infection. searched two databases: National Library Medicine Web Science. Two researchers independently extracted data based specific inclusion exclusion criteria. Results Eighty-three articles were reviewed. categorized four groups: species, models, soluble factors pathways, other molecules (metabolites drugs). M. bovis only studied. P2X7R receptor's higher macrophage recruitment observed differentially after hypervirulent strains. Mice non-human primates (NHPs) most used mammals, emerging like Galleria mellonella planarians also NHPs provided insights into age-dependent immunity markers active (ATB). Key factors/pathways identified included TNF-α, neutrophil recruitment, ROS/RNS responses, autophagy, inflammasomes, antimicrobial peptides, homologous proteins insects. Metabolites vitamin B5 prostaglandin E2 associated Immunomodulatory drugs targeting autophagy mechanisms studied, exhibiting their potential as therapeutic alternatives. Conclusion Simpler, physiologically relevant, ethically sound such G. are needed studying While insects lack adaptive immunity, they could provide “pure” The dissection “pure,” “sustained” (later than 7 days post-infection), trained presents additional challenges require high-resolution temporospatial analytical methods. Identifying targetable pathways blood affected tissues identify biomarkers immunization efficiency, progression, synergistic therapies ATB.

Language: Английский

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Overexpressed Rv0222 in M. smegmatis suppresses host innate immunity by downregulating miR-9 target SIRT1

Microbial Pathogenesis, Journal Year: 2025, Volume and Issue: unknown, P. 107525 - 107525

Published: April 1, 2025

Language: Английский

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