ArticleProceedings of the National Academy of Sciences of the United States of America2019
Specific sequences of infectious challenge lead to secondary hemophagocytic lymphohistiocytosis-like disease in mice.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 67 citations in OpenAlex.
- A novel two-hit murine model of viral-primed sepsis-associated acute kidney injury.American journal of physiology. Renal physiology · 2026Article
- Chimeric antigen receptor T-cell therapies related to immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome: Diagnosis, high-risk factors, and management.Chinese medical journal · 2026Review
- Lysine-11 ubiquitination drives type-I/III interferon induction by cGAS-STING and Toll-like receptors 3 and 4.Nature cell biology · 2026Article
- The Emerging Role of Transcription Factor Spi-C in Macrophage Biology and Inflammatory Pathogenesis.International journal of molecular sciences · 2026Review
- The "cytokine storm" in infection and sepsis: win the battle but lose the war.Military Medical Research · 2026Review
- Effect of anakinra on cytokine storm during sepsis-induced multiple organ dysfunction syndrome: case report and preclinical investigation.Frontiers in immunology · 2026Article
- Interaction networks of macrophage glycolysis and inflammation in sepsis: mechanisms and therapeutic potential.Frontiers in immunology · 2026Review
- The Clinical View of Sepsis-Associated AKI: How Basic Science Can Help Solve This Problem.Seminars in nephrology · 2025Review
- NLRP3 inflammasome-driven hemophagocytic lymphohistiocytosis occurs independent of IL-1β and IL-18 and is targetable by BET inhibitors.Science advances · 2025Article
- Weal and woe of interleukin-18 in the T cell therapy of cancer.Journal for immunotherapy of cancer · 2025Review
- Anti-alcoholism drug disulfiram inhibits PANoptosis by blocking mitochondrial permeabilization in macrophages.Frontiers in immunology · 2025Article
- Alternative mRNA polyadenylation regulates macrophage hyperactivation via the autophagy pathway.Cellular & molecular immunology · 2024Article
- Hemophagocytic lymphohistiocytosis: current treatment advances, emerging targeted therapy and underlying mechanisms.Journal of hematology & oncology · 2024Review
- CircMETTL3-156aa reshapes the glycolytic metabolism of macrophages to promote M1 polarization and induce cytokine storms in sHLH.Cell death discovery · 2024Article
- Pyruvate Kinase M2 Nuclear Translocation Regulate Ferroptosis-Associated Acute Lung Injury in Cytokine Storm.Inflammation · 2024Article
- Low-dose pro-resolving mediators temporally reset the resolution response to microbial inflammation.Molecular medicine (Cambridge, Mass.) · 2024Article
- NLRC5 senses NADCell · 2024Article
- Neutrophil-macrophage communication via extracellular vesicle transfer promotes itaconate accumulation and ameliorates cytokine storm syndrome.Cellular & molecular immunology · 2024Article
- Inflammatory cell death PANoptosis is induced by the anti-cancer curaxin CBL0137 via eliciting the assembly of ZBP1-associated PANoptosome.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Article
- Monocytic Phagocytes in the Immunopathogenesis of Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Secondary hemophagocytic lymphohistiocytosis (sHLH) is a highly mortal complication associated with sepsis. In adults, it is often seen in the setting of infections, especially viral infections, but the mechanisms that underlie pathogenesis are unknown. sHLH is characterized by a hyperinflammatory state and the presence hemophagocytosis. We found that sequential challenging of mice with a nonlethal dose of viral toll-like receptor (TLR) agonist followed by a nonlethal dose of TLR4 agonist, but not other permutations, produced a highly lethal state that recapitulates many aspects of human HLH. We found that this hyperinflammatory response could be recapitulated in vitro in bone marrow-derived macrophages. RNA sequencing analyses revealed dramatic up-regulation of the red-pulp macrophage lineage-defining transcription factor SpiC and its associated transcriptional program, which was also present in bone marrow macrophages sorted from patients with sHLH. Transcriptional profiling also revealed a unique metabolic transcriptional profile in these macrophages, and immunometabolic phenotyping revealed impaired mitochondrial function and oxidative metabolism and a reliance on glycolytic metabolism. Subsequently, we show that therapeutic administration of the glycolysis inhibitor 2-deoxyglucose was sufficient to rescue animals from HLH. Together, these data identify a potential mechanism for the pathogenesis of sHLH and a potentially useful therapeutic strategy for its treatment.
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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.