ArticleThe Journal of clinical investigation2021
WNT6/ACC2-induced storage of triacylglycerols in macrophages is exploited by Mycobacterium tuberculosis.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- PA200 modulates immunoproteasome structure and activity.Nature communications · 2026Article
- Deciphering macrophage dynamics and immune evasion strategies by the intracellular bacteria.Immunologic research · 2025Review
- Diacylglycerol metabolism drives host-pathogen responses during enteric infection inbioRxiv : the preprint server for biology · 2025Article
- Plasma lipidomic analysis reveals distinct lipid alterations in patients with pulmonary tuberculosis.European journal of medical research · 2025Article
- Inducible antibacterial responses in macrophages.Nature reviews. Immunology · 2025Review
- IFN-γ induced the formation of foamy macrophages via CD40 signal to controlFrontiers in immunology · 2025Article
- Diabetes mellitus-driven pulmonary injury: multidimensional mechanisms linking metabolic dysregulation to gut-lung axis and promising therapies.Frontiers in pharmacology · 2025Review
- Repurposed Drugs and Plant-Derived Natural Products as Potential Host-Directed Therapeutic Candidates for Tuberculosis.Biomolecules · 2024Review
- Microbial metabolism disrupts cytokine activity to impact host immune response.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Spatially heterogeneous lipid dysregulation in tuberculous meningitis.Neurobiology of disease · 2024Article
- Fluvastatin Converts Human Macrophages into Foam Cells with Increased Inflammatory Response to InactivatedCells · 2024Article
- Spermine enhances the activity of anti-tuberculosis drugs.Microbiology spectrum · 2024Article
- The Causal Impact of the Gut Microbiota on Respiratory Tuberculosis Susceptibility.Infectious diseases and therapy · 2023Article
- G9a and Sirtuin6 epigenetically modulate host cholesterol accumulation to facilitate mycobacterial survival.PLoS pathogens · 2023Article
- The fat is in the lysosome: how Mycobacterium tuberculosis tricks macrophages into storing lipids.The Journal of clinical investigation · 2023Article
- Host-directed therapy against mycobacterium tuberculosis infections with diabetes mellitus.Frontiers in immunology · 2023Review
- Animal models for COVID-19 and tuberculosis.Frontiers in immunology · 2023Review
- The role ofFrontiers in cellular and infection microbiology · 2023Review
- Mouse Models forPathogens (Basel, Switzerland) · 2022Review
- Host-Directed Therapies for Tuberculosis.Pathogens (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
25 authors at 9 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In view of emerging drug-resistant tuberculosis (TB), host-directed adjunct therapies are urgently needed to improve treatment outcomes with currently available anti-TB therapies. One approach is to interfere with the formation of lipid-laden "foamy" macrophages in the host, as they provide a nutrient-rich host cell environment for Mycobacterium tuberculosis (Mtb). Here, we provide evidence that Wnt family member 6 (WNT6), a ligand of the evolutionarily conserved Wingless/Integrase 1 (WNT) signaling pathway, promotes foam cell formation by regulating key lipid metabolic genes including acetyl-CoA carboxylase 2 (ACC2) during pulmonary TB. Using genetic and pharmacological approaches, we demonstrated that lack of functional WNT6 or ACC2 significantly reduced intracellular triacylglycerol (TAG) levels and Mtb survival in macrophages. Moreover, treatment of Mtb-infected mice with a combination of a pharmacological ACC2 inhibitor and the anti-TB drug isoniazid (INH) reduced lung TAG and cytokine levels, as well as lung weights, compared with treatment with INH alone. This combination also reduced Mtb bacterial numbers and the size of mononuclear cell infiltrates in livers of infected mice. In summary, our findings demonstrate that Mtb exploits WNT6/ACC2-induced storage of TAGs in macrophages to facilitate its intracellular survival, a finding that opens new perspectives for host-directed adjunctive treatment of pulmonary TB.
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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.