ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015
Triggering receptor expressed on myeloid cells-2 fine-tunes inflammatory responses in murine Gram-negative sepsis.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
45 citing papers in PubMed, 68 citations in OpenAlex.
- Assessing the Clinical Relevance of Blood Soluble Triggering Receptor Expressed on Myeloid Cells 2 in Neurological Diseases.The European journal of neuroscience · 2026Observational
- The TREM2 R47H variant is associated with liver-plasma-brain axis dyshomeostasis in the 5xFAD mouse model of Alzheimer's disease.Neurobiology of aging · 2026Article
- TREM2 plays a critical role in innate immune defense against acute Toxoplasma gondii infection by promoting macrophage antimicrobial activities.PLoS pathogens · 2026Article
- Differential downstream signaling in microglia lacking Alzheimer's-related TREM2 or its adaptor TYROBP/DAP12.Molecular neurodegeneration advances · 2026Article
- Targeting Microglial Phagocytosis for Alzheimer's Disease Management: Natural, Pharmacological, Nanoparticle, and Gene Therapy Approaches.CNS & neurological disorders drug targets · 2026Review
- TREM2-apoE3 interactions and Alzheimer's disease: Molecular and structural insights and effects of TREM2 R47H and apoE4 variants.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Unraveling immunosenescence in sepsis: from cellular mechanisms to therapeutics.Cell death & disease · 2025Review
- The role of TREM2 in sepsis. Reply.The Journal of clinical investigation · 2025Article
- Bacterial peptidoglycan levels have brain area, time of day, and sleep loss-induced fluctuations.Frontiers in neuroscience · 2025Article
- Epithelial barrier hypothesis in the context of nutrition, microbial dysbiosis, and immune dysregulation in metabolic dysfunction-associated steatotic liver.Frontiers in immunology · 2025Review
- TREM2Frontiers in immunology · 2025Review
- Transcriptomics changes of calcitonin gene-related peptide in mitigating lipopolysaccharide-induced septic cardiomyopathy.Scientific reports · 2024Article
- TREM2 aggravates sepsis by inhibiting fatty acid oxidation via the SHP1/BTK axis.The Journal of clinical investigation · 2024Article
- Selective targeting and modulation of plaque associated microglia via systemic hydroxyl dendrimer administration in an Alzheimer's disease mouse model.Alzheimer's research & therapy · 2024Article
- Function and mechanism of TREM2 in bacterial infection.PLoS pathogens · 2024Review
- TREM2 Expression and Amyloid-Beta Phagocytosis in Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Consecutive Injection of High-Dose Lipopolysaccharide Modulates Microglia Polarization via TREM2 to Alter Status of Septic Mice.Brain sciences · 2023Article
- Article
- Triggering receptor expressed on myeloid cells-2 promotes survival of cardiomyocytes after myocardial ischemic injury through PI3K/AKT pathway.Cardiovascular diagnosis and therapy · 2022Article
- The Role of Microglia in Alzheimer's Disease From the Perspective of Immune Inflammation and Iron Metabolism.Frontiers in aging neuroscience · 2022Review
Corrections and comments
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Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
Abstract
During infections, TLR-mediated responses require tight regulation to allow for pathogen removal, while preventing overwhelming inflammation and immunopathology. The triggering receptor expressed on myeloid cells (TREM)-2 negatively regulates inflammation by macrophages and impacts on phagocytosis, but the function of endogenous TREM-2 during infections is poorly understood. We investigated TREM-2's role in regulating TLR4-mediated inflammation by studying wild-type and TREM-2(-/-) mice challenged with LPS and found TREM-2 to dampen early inflammation. Augmented early inflammation in TREM-2(-/-) animals was followed by an accelerated resolution and ultimately improved survival, associated with the induction of the negative regulator A20. Upon infection with Escherichia coli, the otherwise beneficial effect of an exaggerated early immune response in TREM-2(-/-) animals was counteracted by a 50% reduction in bacterial phagocytosis. In line with this, TREM-2(-/-) peritoneal macrophages (PMs) exhibited augmented inflammation following TLR4 stimulation, demonstrating the presence and negative regulatory functionality of TREM-2 on primary PMs. Significantly, we identified a high turnover rate because TREM-2 RNA is 25-fold down-regulated and the protein proteasomally degraded upon LPS encounter, thus ensuring a tightly regulated and versatile system that modulates inflammation. Our results illustrate TREM-2's effects on infection-triggered inflammation and identify TREM-2 as a potential target to prevent overwhelming inflammation while preserving antibacterial-effector functions.
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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.