ArticleThe Journal of clinical investigation2020
Post-sepsis immunosuppression depends on NKT cell regulation of mTOR/IFN-γ in NK cells.
Article in The Journal of clinical investigation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 96 citations in OpenAlex.
- Randomized trial of activated vitamin D for acute kidney injury prevention in critically ill patients.JCI insight · 2025Trial
- IFN-γ-Associated Signaling Networks in Interstitial Lung Disease Associated With Sjögren's Disease.Immunity, inflammation and disease · 2026Review
- Epigenetic Mechanisms in Sepsis-Induced Cardiomyopathy: From Pathophysiology to Therapeutic Targets.International journal of molecular sciences · 2026Review
- Disturbed metabolic adaptation drives natural killer cell dysfunction in association with nosocomial infection during human sepsis.EBioMedicine · 2026Article
- Bench-to-Bedside Insights into the Challenges of Immunosuppression in Sepsis.Pathogens (Basel, Switzerland) · 2026Review
- Mitochondrial dysfunction in sepsis-induced immunoparalysis: from immune-cell metabolic reprogramming to clinical biomarkers.Frontiers in immunology · 2026Review
- Lymphocyte function inhibition and exhaustion in sepsis: mechanisms and applications.Frontiers in immunology · 2026Review
- Cetirizine and Dexamethasone in Sepsis: Insights into Maresin-1 Signaling and Cytokine Regulation.Journal of clinical medicine · 2025Article
- IFNγ in human sepsis: a scoping review.Annals of intensive care · 2025Review
- Bioinformatics Approach to Identifying Molecular Targets of Isoliquiritigenin Affecting Chronic Obstructive Pulmonary Disease: A Machine Learning Pharmacology Study.International journal of molecular sciences · 2025Article
- Calorie restriction increases the sensitivity of progeroid Ercc1GeroScience · 2025Article
- The Impact of Steatotic Liver Disease on Cytokine and Chemokine Kinetics During Sepsis.International journal of molecular sciences · 2025Article
- Systemic infection by Candida albicans requires FASN-α subunit induced cell wall remodeling to perturb immune response.PLoS pathogens · 2025Article
- Establishment of a Mouse Intravenous Challenge Model for Predicting Virulence in Yarrowia lipolytica Disseminated Infection.Mycopathologia · 2025Article
- Targeting the immuno-inflammatory-microbial network: a key strategy for sepsis treatment.Frontiers in immunology · 2025Review
- Sepsis and post-sepsis syndrome: a multisystem challenge requiring comprehensive care and management-a review.Frontiers in medicine · 2025Review
- Decoding Sepsis: Unraveling Key Signaling Pathways for Targeted Therapies.Research (Washington, D.C.) · 2025Review
- Adaptation of Natural Killer Cells to Hypoxia: A Review of the Transcriptional, Translational, and Metabolic Processes.ImmunoTargets and therapy · 2025Review
- The Emerging Roles and Therapeutic Potential of Unconventional T Cells in Sepsis.Journal of inflammation research · 2025Review
- Article
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
As treatment of the early, inflammatory phase of sepsis improves, post-sepsis immunosuppression and secondary infection have increased in importance. How early inflammation drives immunosuppression remains unclear. Although IFN-γ typically helps microbial clearance, we found that increased plasma IFN-γ in early clinical sepsis was associated with the later development of secondary Candida infection. Consistent with this observation, we found that exogenous IFN-γ suppressed macrophage phagocytosis of zymosan in vivo, and antibody blockade of IFN-γ after endotoxemia improved survival of secondary candidemia. Transcriptomic analysis of innate lymphocytes during endotoxemia suggested that NKT cells drove IFN-γ production by NK cells via mTORC1. Activation of invariant NKT (iNKT) cells with glycolipid antigen drove immunosuppression. Deletion of iNKT cells in Cd1d-/- mice or inhibition of mTOR by rapamycin reduced immunosuppression and susceptibility to secondary Candida infection. Thus, although rapamycin is typically an immunosuppressive medication, in the context of sepsis, rapamycin has the opposite effect. These results implicated an NKT cell/mTOR/IFN-γ axis in immunosuppression following endotoxemia or sepsis. In summary, in vivo iNKT cells activated mTORC1 in NK cells to produce IFN-γ, which worsened macrophage phagocytosis, clearance of secondary Candida infection, and mortality.
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Registered trials
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