ArticleThe Journal of clinical investigation2021
TREM-2 promotes Th1 responses by interacting with the CD3ζ-ZAP70 complex following Mycobacterium tuberculosis infection.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers, 1 of them a synthesis that pooled it.
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Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Systematic review of innate immune responses againstFrontiers in immunology · 2024Pooled it
- TREM2 plays a critical role in innate immune defense against acute Toxoplasma gondii infection by promoting macrophage antimicrobial activities.PLoS pathogens · 2026Article
- TREM2 Regulates Microglial Activation via the ERK/p38 Signaling Pathway: Implications for the Pathogenesis of Experimental Autoimmune Uveitis.Investigative ophthalmology & visual science · 2026Article
- Decoding TREM2 Signaling Pathways: Linking Macrophage Glycolysis to Inflammatory Diseases in the CNS.Neurology(R) neuroimmunology & neuroinflammation · 2026Review
- Decoding macrophage heterogeneity in the pulmonary fibrosis lung cancer transition.Frontiers in immunology · 2026Review
- Macrophage states and polarization duringFrontiers in cellular and infection microbiology · 2026Review
- TREM2 signaling pathway in sepsis-induced acute lung injury: physiology, pathology, and therapeutic applications.Frontiers in medicine · 2025Review
- Glycogen synthase kinase 3 inhibition controlsiScience · 2024Article
- TREM2 mediates MHCII-associated CD4+ T-cell response against gliomas.Neuro-oncology · 2024Article
- TREM2 function in glioblastoma immune microenvironment: Can we distinguish reality from illusion?Neuro-oncology · 2024Article
- Triggering Receptor Expressed on Myeloid Cells 2 Mediates the Involvement of M2-Type Macrophages in Pulmonary Tuberculosis Infection.Journal of inflammation research · 2024Article
- TREM-2 Drives Development of Multiple Sclerosis by Promoting Pathogenic Th17 Polarization.Neuroscience bulletin · 2024Article
- Hepatic lipid-associated macrophages mediate the beneficial effects of bariatric surgery against MASH.Research square · 2023Article
- Role of pattern recognition receptors in sensingHeliyon · 2023Review
- TREM2 mediates MHCII-associated CD4bioRxiv : the preprint server for biology · 2023Article
- TREM-1, TREM-2 and their association with disease severity in patients with COVID-19.Annals of medicine · 2023Article
- Impact of aging on immunity in the context of COVID-19, HIV, and tuberculosis.Frontiers in immunology · 2023Review
- Identification of Novel Kinases of Tau Using Fluorescence Complementation Mass Spectrometry (FCMS).Molecular & cellular proteomics : MCP · 2022Article
- Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination.Journal of neuroinflammation · 2022Article
- Article
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Authors and funding
16 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triggering receptor expressed on myeloid cells 2 (TREM-2) is a modulator of pattern recognition receptors on innate immune cells that regulates the inflammatory response. However, the role of TREM-2 in in vivo models of infection and inflammation remains controversial. Here, we demonstrated that TREM-2 expression on CD4+ T cells was induced by Mycobacterium tuberculosis infection in both humans and mice and positively associated with T cell activation and an effector memory phenotype. Activation of TREM-2 in CD4+ T cells was dependent on interaction with the putative TREM-2 ligand expressed on DCs. Unlike the observation in myeloid cells that TREM-2 signals through DAP12, in CD4+ T cells, TREM-2 interacted with the CD3ζ-ZAP70 complex as well as with the IFN-γ receptor, leading to STAT1/-4 activation and T-bet transcription. In addition, an infection model using reconstituted Rag2-/- mice (with TREM-2-KO vs. WT cells or TREM-2+ vs. TREM-2-CD4+ T cells) or CD4+ T cell-specific TREM-2 conditional KO mice demonstrated that TREM-2 promoted a Th1-mediated host defense against M. tuberculosis infection. Taken together, these findings reveal a critical role of TREM-2 in evoking proinflammatory Th1 responses that may provide potential therapeutic targets for infectious and inflammatory diseases.
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