ArticleProceedings of the National Academy of Sciences of the United States of America2013
TREM2 governs Kupffer cell activation and explains belr1 genetic resistance to malaria liver stage infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 49 citations in OpenAlex.
- 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 drives monocyte-derived macrophage responses tobioRxiv : the preprint server for biology · 2026Article
- Hepatocyte-Derived Apoptotic Bodies as Pathological Intercellular Messengers in the Liver.Biomolecules · 2026Review
- Interplay between CD33 and TREM2 in Alzheimer's Disease: Potential Mechanistic Insights into Microglial Function in Amyloid Pathology.ACS chemical neuroscience · 2026Review
- Trem2 negatively regulates the MTOR-PKCα axis to protect againstFrontiers in cellular and infection microbiology · 2026Article
- 3D co-cultures of primary human hepatocytes and Kupffer-like cells to address innate immune responses to rAAV.Scientific reports · 2025Article
- Toxoplasma gondii-induced adverse pregnancy outcomes: insight into the inhibitory role of Trem2 on TLR4/TRAF6/JNK signaling pathway.Parasites & vectors · 2025Article
- Role of triggering receptor expressed on myeloid cells 2 in the pathogenesis of non-alcoholic fatty liver disease.World journal of hepatology · 2025Review
- TREM2Frontiers in immunology · 2025Review
- Trem2/Syk/PI3K axis contributes to the host protection against Toxoplasma gondii-induced adverse pregnancy outcomes via modulating decidual macrophages.PLoS pathogens · 2024Article
- Myeloid Trem2 Dynamically Regulates the Induction and Resolution of Hepatic Ischemia-Reperfusion Injury Inflammation.International journal of molecular sciences · 2023Article
- Trem2 deficiency impairs recovery and phagocytosis and dysregulates myeloid gene expression during virus-induced demyelination.Journal of neuroinflammation · 2022Article
- The therapeutic potential of TREM2 in cancer.Frontiers in oncology · 2022Review
- Factors influencing phagocytosis of malaria parasites: the story so far.Malaria journal · 2021Review
- TREM2: Keeping Pace With Immune Checkpoint Inhibitors in Cancer Immunotherapy.Frontiers in immunology · 2021Review
- Impact of Galectin-Receptor Interactions on Liver Pathology During the Erythrocytic Stage ofFrontiers in immunology · 2021Article
- Review
- TREM2 suppresses the proinflammatory response to facilitate PRRSV infection via PI3K/NF-κB signaling.PLoS pathogens · 2020Article
- Trem-2 Promotes Emergence of Restorative Macrophages and Endothelial Cells During Recovery From Hepatic Tissue Damage.Frontiers in immunology · 2020Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Plasmodium liver stage infection is a target of interest for the treatment of and vaccination against malaria. Here we used forward genetics to search for mechanisms underlying natural host resistance to infection and identified triggering receptor expressed on myeloid cells 2 (TREM2) and MHC class II molecules as determinants of Plasmodium berghei liver stage infection in mice. Locus belr1 confers resistance to malaria liver stage infection. The use of newly derived subcongenic mouse lines allowed to map belr1 to a 4-Mb interval on mouse chromosome 17 that contains the Trem2 gene. We show that Trem2 expression in the nonparenchymal liver cells closely correlates with resistance to liver stage infection, implicating TREM2 as a mediator of the belr1 genetic effect. Trem2-deficient mice are more susceptible to liver stage infection than their WT counterparts. We found that Kupffer cells are the principle cells expressing TREM2 in the liver, and that Trem2(-/-) Kupffer cells display altered functional activation on exposure to P. berghei sporozoites. TREM2 expression in Kupffer cells contributes to the limitation of parasite expansion in isolated hepatocytes in vitro, potentially explaining the increased susceptibility of Trem2(-/-) mice to liver stage infection. The MHC locus was also found to control liver parasite burden, possibly owing to the expression of MHC class II molecules in hepatocytes. Our findings implicate unexpected Kupffer-hepatocyte cross-talk in the control Plasmodium liver stage infection and demonstrate that TREM2 is involved in host responses against the malaria parasite.
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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.