ArticlePLoS pathogens2018
Macrophage migration inhibitory factor is critical for dengue NS1-induced endothelial glycocalyx degradation and hyperpermeability.
Article in PLoS pathogens, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 83 citations in OpenAlex.
- Temporal Rewiring of Innate Immunity by Vector-Borne Viruses for Host-Directed Antiviral Therapy.International journal of molecular sciences · 2026Review
- P2Y12-P-selectin-mediated platelet activation in a murine model of dengue-associated thrombocytopenia.EBioMedicine · 2026Article
- Pericyte dysfunction alone may be insufficient to drive tick-borne orthoflavivirus non-structural protein 1-mediated microvascular permeability.The Journal of general virology · 2026Article
- Dengue NS1 as a Driver of Immune-Mediated Pathogenesis.Tropical medicine and infectious disease · 2026Review
- The dengue virus NS1 protein altersmBio · 2026Article
- Macrophage migration inhibitory factor (MIF): a Janus-faced cytokine in viral pathogenesis and host defense.Immunologic research · 2025Review
- Pathogenesis and clinical management of arboviral diseases.World journal of virology · 2025Review
- Echinocystic acid inFrontiers in medicine · 2025Article
- Japanese encephalitis virus NS1 and NS1' protein disrupts the blood-brain barrier through macrophage migration inhibitory factor-mediated autophagy.Journal of virology · 2024Article
- Capillary leak and endothelial permeability in critically ill patients: a current overview.Intensive care medicine experimental · 2023Review
- The Role of Macrophage Migration Inhibitory Factor (MIF) and D-Dopachrome Tautomerase (D-DT/MIF-2) in Infections: A Clinical Perspective.Biomedicines · 2023Review
- Serum biomarkers and anti-flavivirus antibodies at presentation as indicators of severe dengue.PLoS neglected tropical diseases · 2023Article
- Secretory pathways and multiple functions of nonstructural protein 1 in flavivirus infection.Frontiers in immunology · 2023Review
- Unbiased Identification of Dengue Virus Non-Structural Protein 1 Peptides for Use in Vaccine Design.Vaccines · 2022Article
- Pharmacotherapy consideration of thrombolytic medications in COVID-19-associated ARDS.Journal of intensive care · 2022Review
- Flavivirus NS1 Triggers Tissue-Specific Disassembly of Intercellular Junctions Leading to Barrier Dysfunction and Vascular Leak in a GSK-3β-Dependent Manner.Pathogens (Basel, Switzerland) · 2022Article
- Subsets of Cytokines and Chemokines from DENV-4-Infected Patients Could Regulate the Endothelial Integrity of Cultured Microvascular Endothelial Cells.Pathogens (Basel, Switzerland) · 2022Article
- Evaluation of a new NS1 rapid diagnostic test using a single acute-phase serum panel collected during the largest dengue outbreak in Taiwan history in 2015.The Kaohsiung journal of medical sciences · 2022Article
- Rescue therapy with intravenous immunoglobulin in severe refractory dengue: A pilot study.Medical journal, Armed Forces India · 2022Article
- Therapeutic efficacy of humanized monoclonal antibodies targeting dengue virus nonstructural protein 1 in the mouse model.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Vascular leakage is one of the salient characteristics of severe dengue. Nonstructural protein 1 (NS1) of dengue virus (DENV) can stimulate endothelial cells to secrete endothelial hyperpermeability factor, macrophage migration inhibitory factor (MIF), and the glycocalyx degradation factor heparanase 1 (HPA-1). However, it is unclear whether MIF is directly involved in NS1-induced glycocalyx degradation. In this study, we observed that among NS1, MIF and glycocalyx degradation-related molecules, the HPA-1, metalloproteinase 9 (MMP-9) and syndecan 1 (CD138) serum levels were all increased in dengue patients, and only NS1 and MIF showed a positive correlation with the CD138 level in severe patients. To further characterize and clarify the relationship between MIF and CD138, we used recombinant NS1 to stimulate human cells in vitro and challenge mice in vivo. Our tabulated results suggested that NS1 stimulation could induce human endothelial cells to secrete HPA-1 and immune cells to secrete MMP-9, resulting in endothelial glycocalyx degradation and hyperpermeability. Moreover, HPA-1, MMP-9, and CD138 secretion after NS1 stimulation was blocked by MIF inhibitors or antibodies both in vitro and in mice. Taken together, these results suggest that MIF directly engages in dengue NS1-induced glycocalyx degradation and that targeting MIF may represent a possible therapeutic approach for preventing dengue-induced vascular leakage.
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