ArticleJCI insight2019
TLR9/MyD88/TRIF signaling activates host immune inhibitory CD200 in Leishmania infection.
Article in JCI insight, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Revisiting the past in light of current knowledge on γδ T cells in leishmaniasis.Frontiers in immunology · 2026Review
- Stage-Specific Expression and Subcellular Localization of Calcineurin in Infective Forms ofPathogens (Basel, Switzerland) · 2025Article
- Leishmania amazonensis impairs phagosome acidification in B-1 phagocytes as an unrecognized parasite infection and proliferation mechanism.Scientific reports · 2025Article
- Roles of TLR9: Gatekeeper to fungal infections.PLoS pathogens · 2025Article
- Unleashing the immune modulatory potential ofFrontiers in molecular biosciences · 2025Article
- Immunotherapeutic Strategies as Potential Treatment Options for Cutaneous Leishmaniasis.Vaccines · 2024Review
- TIRAP, TRAM, and Toll-Like Receptors: The Untold Story.Mediators of inflammation · 2023Review
- When the allergy alarm bells toll: The role of Toll-like receptors in allergic diseases and treatment.Frontiers in molecular biosciences · 2023Review
- Transcriptional profiling of macrophages reveals distinct parasite stage-driven signatures during early infection by Leishmania donovani.Scientific reports · 2022Article
- Paradoxical immune response in leishmaniasis: The role of toll-like receptors in disease progression.Parasite immunology · 2022Review
- CASP-Model Sepsis Triggers Systemic Innate Immune Responses Revealed by the Systems-Level Signaling Pathways.Frontiers in immunology · 2022Article
- In Silico Characterization of Calcineurin from Pathogenic Obligate Intracellular Trypanosomatids: Potential New Biological Roles.Biomolecules · 2021Article
- Potential therapeutic targets shared between leishmaniasis and cancer.Parasitology · 2021Review
- Immunosuppression and Neuroinflammation in Stroke Pathobiology.Experimental neurobiology · 2021Review
- CD200:CD200R Interactions and Their Importance in Immunoregulation.International journal of molecular sciences · 2021Review
- Long-TermJournal of immunology research · 2021Article
- The Paradox of a Phagosomal Lifestyle: How Innate Host Cell-Frontiers in immunology · 2021Review
- Mechanisms of Immunopathogenesis in Cutaneous Leishmaniasis And Post Kala-azar Dermal Leishmaniasis (PKDL).Frontiers in cellular and infection microbiology · 2021Review
- Unraveling the Role of Immune Checkpoints in Leishmaniasis.Frontiers in immunology · 2021Review
- Effect of DODAB Nano-Sized Cationic Bilayer Fragments againstMolecules (Basel, Switzerland) · 2020Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Virulent protozoans named Leishmania in tropical and subtropical areas produce devastating diseases by exploiting host immune responses. Amastigotes of Leishmania amazonensis stimulate macrophages to express CD200, an immunomodulatory ligand, which binds to its cognate receptor (CD200R) and inhibits the inducible nitric oxide synthase and nitric oxide (iNOS/NO) signaling pathways, thereby promoting intracellular survival. However, the mechanisms underlying CD200 induction in macrophages remain largely unknown. Here, we show that phagocytosis-mediated internalization of L. amazonensis amastigotes following activation of endosomal TLR9/MyD88/TRIF signaling is critical for inducing CD200 in infected macrophages. We also demonstrate that Leishmania microvesicles containing DNA fragments activate TLR9-dependent CD200 expression, which inhibits the iNOS/NO pathway and modulates the course of L. amazonensis infection in vivo. These findings demonstrate that Leishmania exploits TLR-signaling pathways not only to inhibit macrophage microbicidal function, but also to evade host systemic immune responses, which has many implications in the severity of the disease.
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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.