ArticleThe American journal of pathology2010
Activation of phosphatidylinositol 3-kinase/Akt and impairment of nuclear factor-kappaB: molecular mechanisms behind the arrested maturation/activation state of Leishmania infantum-infected dendritic cells.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 44 citations in OpenAlex.
- Persistent myeloid cell reprogramming despite miltefosine treatment in leishmania-infected macaques.iScience · 2025Article
- Targeting NRF2 With Isoeugenol: A Promising Small Molecule for Neurodegenerative, Metabolic, and Chronic Inflammatory Disorders.Oxidative medicine and cellular longevity · 2025Review
- Human Dendritic Cell Maturation Is Modulated byTropical medicine and infectious disease · 2024Article
- ExploitingCells · 2024Article
- Transcriptional Profiling ofMicroorganisms · 2022Article
- The Role of Nuclear Factor Kappa B (NF-κB) in the Immune Response against Parasites.Pathogens (Basel, Switzerland) · 2022Review
- Co-Administration of Anticancer Candidate MK-2206 Enhances the Efficacy of BCG Vaccine AgainstFrontiers in immunology · 2021Article
- Runx proteins mediate protective immunity against Leishmania donovani infection by promoting CD40 expression on dendritic cells.PLoS pathogens · 2020Article
- Giardia lamblia Decreases NF-κB p65Scientific reports · 2020Article
- TLR4 abrogates the Th1 immune response through IRF1 and IFN-β to prevent immunopathology during L. infantum infection.PLoS pathogens · 2020Article
- Article
- Evaluation of synergy between host and pathogen-directed therapies against intracellular Leishmania donovani.International journal for parasitology. Drugs and drug resistance · 2019Article
- Review
- More than just exosomes: distinctJournal of extracellular vesicles · 2019Article
- Review
- Immune Checkpoint Targets for Host-Directed Therapy to Prevent and Treat Leishmaniasis.Frontiers in immunology · 2017Review
- Leishmania donovani inhibits macrophage apoptosis and pro-inflammatory response through AKT-mediated regulation of β-catenin and FOXO-1.Cell death and differentiation · 2016Article
- Host-mediated Leishmania donovani treatment using AR-12 encapsulated in acetalated dextran microparticles.International journal of pharmaceutics · 2016Article
- Interleukin-27 Early ImpactsFrontiers in immunology · 2016Article
- Leishmania infantum and Leishmania braziliensis: Differences and Similarities to Evade the Innate Immune System.Frontiers in immunology · 2016Article
Corrections and comments
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Understanding the complex interactions between Leishmania and dendritic cells (DCs) is central to the modulation of the outcome of this infection, given that an effective immune response against Leishmania is dependent on the successful activation and maturation of DCs. We report here that Leishmania infantum promastigotes successfully infect mouse bone marrow-derived DCs without triggering maturation, as shown by a failure in the up-regulation of CD40 and CD86 expression, and that parasites strongly counteract the lipopolysaccharide-triggered maturation of DCs. A small increase in interleukin (IL)-12 and IL-10 transcription and secretion and a decrease in IL-6 were observed in infected cells. This arrested DC maturation state is actively promoted by parasites because heat-killed or fixed parasites increased cytokine and costimulatory molecule expression. At a molecular level, L. infantum rapidly induced activation of phosphatidylinositol 3-kinase/Akt and extracellular signal-regulated kinase 1/2, whereas no effect was observed in the c-Jun N-terminal kinase and p38 mitogen-activated protein kinase proinflammatory pathways. Moreover, parasites actively promoted cleavage of the nuclear factor-κB p65(RelA) subunit, causing its impairment. The blockade of phosphatidylinositol 3-kinase/Akt by either treatment of bone marrow-derived DCs with wortmannin or transfection with an Akt dominant-negative mutant resulted in a strong decrease in infection rates, revealing for the first time a crucial role of this pathway on Leishmania engulfment by DCs. Overall, our data indicate that activation of Akt and impairment of nuclear factor-κB are responsible for immunogenicity subversion of L. infantum-infected DCs.
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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.