ArticlePloS one2011
Mycobacterial PIMs inhibit host inflammatory responses through CD14-dependent and CD14-independent mechanisms.
Article in PloS one, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Mechanistic studies of mycobacterial glycolipid biosynthesis by the mannosyltransferase PimE.Nature communications · 2025Article
- Zinc-limitedInfection and immunity · 2025Article
- Immunological hyporesponsiveness in tuberculosis: The role of mycobacterial glycolipids.Frontiers in immunology · 2022Review
- Chemical Synthesis of Cell Wall Constituents ofChemical reviews · 2021Review
- Silver Nanoparticles for the Therapy of Tuberculosis.International journal of nanomedicine · 2020Review
- The Two-Component Locus MSMEG_0244/0246 Together With MSMEG_0243 Affects Biofilm Assembly inFrontiers in microbiology · 2020Article
- HIV Disclosure and Transmission Risks to Sex Partners Among HIV-Positive Men.AIDS patient care and STDs · 2016Article
- Ac2PIM-responsive miR-150 and miR-143 target receptor-interacting protein kinase 2 and transforming growth factor beta-activated kinase 1 to suppress NOD2-induced immunomodulators.The Journal of biological chemistry · 2015Article
- Soluble human TLR2 ectodomain binds diacylglycerol from microbial lipopeptides and glycolipids.Innate immunity · 2015Article
- Highly purified mycobacterial phosphatidylinositol mannosides drive cell-mediated responses and activate NKT cells in cattle.Clinical and vaccine immunology : CVI · 2015Article
- Porphyromonas gingivalis gingipains selectively reduce CD14 expression, leading to macrophage hyporesponsiveness to bacterial infection.Journal of innate immunity · 2015Article
- Role of toll-interacting protein gene polymorphisms in leprosy Mexican patients.BioMed research international · 2013Article
- Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mycobacteria develop strategies to evade the host immune system. Among them, mycobacterial LAM or PIMs inhibit the expression of pro-inflammatory cytokines by activated macrophages. Here, using synthetic PIM analogues, we analyzed the mode of action of PIM anti-inflammatory effects. Synthetic PIM(1) isomer and PIM(2) mimetic potently inhibit TNF and IL-12 p40 expression induced by TLR2 or TLR4 pathways, but not by TLR9, in murine macrophages. We show inhibition of LPS binding to TLR4/MD2/CD14 expressing HEK cells by PIM(1) and PIM(2) analogues. More specifically, the binding of LPS to CD14 was inhibited by PIM(1) and PIM(2) analogues. CD14 was dispensable for PIM(1) and PIM(2) analogues functional inhibition of TLR2 agonists induced TNF, as shown in CD14-deficient macrophages. The use of rough-LPS, that stimulates TLR4 pathway independently of CD14, allowed to discriminate between CD14-dependent and CD14-independent anti-inflammatory effects of PIMs on LPS-induced macrophage responses. PIM(1) and PIM(2) analogues inhibited LPS-induced TNF release by a CD14-dependent pathway, while IL-12 p40 inhibition was CD14-independent, suggesting that PIMs have multifold inhibitory effects on the TLR4 signalling pathway.
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Registered trials
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.