Targeting Autophagy as a Strategy for Developing New Host-Directed Therapeutics Against Nontuberculous Mycobacteria DOI Creative Commons
Jia Wang, Sunhee Lee

Pathogens, Journal Year: 2025, Volume and Issue: 14(5), P. 472 - 472

Published: May 13, 2025

Nontuberculous mycobacteria (NTMs) are increasingly being recognized as opportunistic pathogens in clinical practice because of their innate resistance to antimicrobial treatment and the widespread increase multidrug-resistant strains on a global scale. NTMs pose tremendous infection management challenge, especially individuals with pre-existing lung conditions, well those who immunocompromised. NTMs' capability evade or suppress immune responses host is key feature that makes them cause persistent chronic infection. Autophagy, an essential cellular defense mechanism delivers breaks down intracellular materials lysosomes, protects from mycobacterial Initial studies have revealed encouraging therapeutic strategies augment endogenous autophagic mechanisms block harmful responses, thus having potential decrease infection, including caused by strains. This review discusses how can considers possibilities using autophagy-inducing agents develop novel combat NTM

Language: Английский

Inducible antibacterial responses in macrophages DOI
Matthew J. Sweet, Divya Ramnath, Amit Singhal

et al.

Nature reviews. Immunology, Journal Year: 2024, Volume and Issue: 25(2), P. 92 - 107

Published: Sept. 18, 2024

Language: Английский

Citations

19
Autophagy prevents early proinflammatory responses and neutrophil recruitment during Mycobacterium tuberculosis infection without affecting pathogen burden in macrophages DOI Creative Commons
Rachel L. Kinsella, Jacqueline M. Kimmey, Asya Smirnov

et al.

PLoS Biology, Journal Year: 2023, Volume and Issue: 21(6), P. e3002159 - e3002159

Published: June 15, 2023

The immune response to Mycobacterium tuberculosis infection determines disease outcomes, yet we have an incomplete understanding of what factors contribute a protective response. Neutrophilic inflammation has been associated with poor prognosis in humans and animal models during M. and, therefore, must be tightly regulated. ATG5 is essential autophagy protein that required innate cells control neutrophil-dominated promote survival infection; however, the mechanistic basis for how regulates neutrophil recruitment unknown. To interrogate require infection, used different mouse strains conditionally delete Atg5 specific cell types. We found CD11c+ (lung macrophages dendritic cells) production proinflammatory cytokines chemokines which would otherwise recruitment. This role dependent, but independent mitophagy, LC3-associated phagocytosis, inflammasome activation, are most well-characterized ways proteins regulate inflammation. In addition increased cytokine from loss also results early induction TH17 responses. Despite prior published vitro culture experiments supporting controlling replication macrophages, effects on inflammatory responses occur without changes burden macrophages. These findings reveal new roles lung resident suppress infection.

Language: Английский

Citations

25
PPARG-mediated autophagy activation alleviates inflammation in rheumatoid arthritis DOI

Qishun Geng,

Jiahe Xu,

Xiaoxue Cao

et al.

Journal of Autoimmunity, Journal Year: 2024, Volume and Issue: 146, P. 103214 - 103214

Published: April 21, 2024

Language: Английский

Citations

14
Autophagy promotes efficient T cell responses to restrict high-dose Mycobacterium tuberculosis infection in mice DOI
Siwei Feng, Michael E. McNehlan, Rachel L. Kinsella

et al.

Nature Microbiology, Journal Year: 2024, Volume and Issue: 9(3), P. 684 - 697

Published: Feb. 27, 2024

Language: Английский

Citations

10
ATG9A facilitates the closure of mammalian autophagosomes DOI
Ruheena Javed, Muriel Mari, Einar S Trosdal

et al.

The Journal of Cell Biology, Journal Year: 2025, Volume and Issue: 224(2)

Published: Jan. 2, 2025

Canonical autophagy captures within specialized double-membrane organelles, termed autophagosomes, an array of cytoplasmic components destined for lysosomal degradation. An autophagosome is completed when the growing phagophore undergoes ESCRT-dependent membrane closure, a prerequisite its subsequent fusion with endolysosomal organelles and degradation sequestered cargo. ATG9A, key integral protein pathway, best known role in formation expansion phagophores. Here, we report hitherto unappreciated function mammalian ATG9A directing closure. partners IQGAP1 ESCRT-III component CHMP2A to facilitate this final stage formation. Thus, central hub governing all major aspects biogenesis, from unique ATG factor progressive functionalities affecting physiological outputs autophagy.

Language: Английский

Citations

2
Noncanonical roles of ATG5 and membrane atg8ylation in retromer assembly and function DOI Creative Commons

Masroor Ahmad Paddar,

Fulong Wang, Einar S Trosdal

et al.

eLife, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 7, 2025

ATG5 is one of the core autophagy proteins with additional functions such as noncanonical membrane atg8ylation, which among a growing number biological outputs includes control tuberculosis in animal models. Here, we show that associates retromer’s components VPS26, VPS29, and VPS35 modulates retromer function. Knockout blocked trafficking key glucose transporter sorted by retromer, GLUT1, to plasma membrane. Knockouts other genes essential for component, affected GLUT1 sorting, indicating atg8ylation process affects function endosomal sorting. The contribution sorting was independent canonical autophagy. These findings expand scope specific processes cell dependent on its known interactors.

Language: Английский

Citations

2
Advances in Host–Pathogen Interactions in Tuberculosis: Emerging Strategies for Therapeutic Intervention DOI Open Access
Mohammad Javad Nasiri, Vishwanath Venketaraman

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(4), P. 1621 - 1621

Published: Feb. 14, 2025

Tuberculosis (TB) remains one of the most challenging infectious diseases, with Mycobacterium tuberculosis (Mtb) employing sophisticated mechanisms to evade host immunity and establish persistent infections. This review explores recent advances in understanding Mtb's immune evasion strategies; granuloma dynamics; emerging immunotherapeutic approaches. Key findings highlight manipulation autophagy; metabolic reprogramming; cytokine pathways by Mtb sustain its survival within cells. Insights into formation reveal critical role bacterial lipids; modulation; hypoxia-driven dormancy maintaining chronic infection. Innovative therapeutic strategies, including host-directed therapies; epigenetic interventions; immunomodulators, hold promise for improving TB management combating drug-resistant strains. Despite these advancements, significant challenges remain, development effective vaccines; addressing latent TB; ensuring equitable access novel treatments. The integration advanced technologies such as artificial intelligence multi-omics approaches, alongside global collaboration, is essential overcome hurdles. underscores importance a multidisciplinary approach tackling TB, ultimate goal eradicating this health threat.

Language: Английский

Citations

1
cGAS-mediated Antibacterial Immunotherapy Against Tuberculosis by Macrophage-Targeted Manganese Dioxide Nanoagonist DOI

Kangsheng Liao,

Ruihong Chen, Jinwei Zhang

et al.

Acta Biomaterialia, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

1
Autophagy is part of the answer to tuberculosis DOI Open Access
Vojo Deretić, Fulong Wang

Nature Microbiology, Journal Year: 2023, Volume and Issue: 8(5), P. 762 - 763

Published: May 4, 2023

Language: Английский

Citations

17
The ubiquitin ligase TRIM32 promotes the autophagic response to Mycobacterium tuberculosis infection in macrophages DOI Creative Commons
Alessandra Romagnoli, Martina Di Rienzo, Elisa Petruccioli

et al.

Cell Death and Disease, Journal Year: 2023, Volume and Issue: 14(8)

Published: Aug. 5, 2023

Mycobacterium tuberculosis (Mtb) is known to evade host immune responses and persist in macrophages for long periods. A mechanism that the uses combat Mtb xenophagy, a selective form of autophagy targets intracellular pathogens degradation. Ubiquitination or Mtb-containing compartments key event recruit machinery mediate bacterial delivery lysosome. This relies on coordinated complementary activity different ubiquitin ligases, including PARKIN, SMURF1, TRIM16. Because each these factors responsible ubiquitination subset population, it likely additional ligases are employed by trigger full xenophagic response during infection. In this study, we investigated role TRIM proteins whose expression modulated BCG infection primary macrophages. These TRIMs were ectopically expressed THP1 macrophage cell line assess their impact replication. screening identified TRIM32 as novel player involved infection, which promotes autophagy-mediated The xenophagy was further confirmed silencing cells, causes increased growth associated impaired ubiquitination, reduced recruitment NDP52/CALCOCO2 BECLIN 1/BECN1 autophagosome formation. Overall, findings suggest plays an important through induction autophagy, representing promising target host-directed therapies.

Language: Английский

Citations

14