Colonna M. TREMs in the immune system and beyond. Nat Rev Immunol. 2003;3:445–53.

CAS  PubMed  Google Scholar 

Yeh FL, Hansen DV, Sheng M. TREM2, microglia, and neurodegenerative diseases. Trends Mol Med. 2017;23:512–33.

CAS  PubMed  Google Scholar 

Jay TR, von Saucken VE, Landreth GE. TREM2 in neurodegenerative diseases. Mol Neurodegener. 2017;12:56.

PubMed  PubMed Central  Google Scholar 

Painter MM, Atagi Y, Liu CC, Rademakers R, Xu H, Fryer JD, Bu G. TREM2 in CNS homeostasis and neurodegenerative disease. Mol Neurodegener. 2015;10:43.

PubMed  PubMed Central  Google Scholar 

Deczkowska A, Weiner A, Amit I. The physiology, pathology, and potential therapeutic applications of the TREM2 signaling pathway. Cell. 2020;181:1207–17.

CAS  PubMed  Google Scholar 

Fu R, Shen Q, Xu P, Luo JJ, Tang Y. Phagocytosis of microglia in the central nervous system diseases. Mol Neurobiol. 2014;49:1422–34.

CAS  PubMed  PubMed Central  Google Scholar 

Cantoni C, Bollman B, Licastro D, Xie M, Mikesell R, Schmidt R, Yuede CM, Galimberti D, Olivecrona G, Klein RS, et al. TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol. 2015;129:429–47.

CAS  PubMed  PubMed Central  Google Scholar 

Piccio L, Buonsanti C, Mariani M, Cella M, Gilfillan S, Cross AH, Colonna M, Panina-Bordignon P. Blockade of TREM-2 exacerbates experimental autoimmune encephalomyelitis. Eur J Immunol. 2007;37:1290–301.

CAS  PubMed  Google Scholar 

Poliani PL, Wang Y, Fontana E, Robinette ML, Yamanishi Y, Gilfillan S, Colonna M. TREM2 sustains microglial expansion during aging and response to demyelination. J Clin Invest. 2015;125:2161–70.

PubMed  PubMed Central  Google Scholar 

Cignarella F, Filipello F, Bollman B, Cantoni C, Locca A, Mikesell R, Manis M, Ibrahim A, Deng L, Benitez BA, et al. TREM2 activation on microglia promotes myelin debris clearance and remyelination in a model of multiple sclerosis. Acta Neuropathol. 2020;140:513–34.

CAS  PubMed  PubMed Central  Google Scholar 

Takahashi K, Prinz M, Stagi M, Chechneva O, Neumann H. TREM2-transduced myeloid precursors mediate nervous tissue debris clearance and facilitate recovery in an animal model of multiple sclerosis. PLoS Med. 2007;4:e124.

PubMed  PubMed Central  Google Scholar 

Wu K, Byers DE, Jin X, Agapov E, Alexander-Brett J, Patel AC, Cella M, Gilfilan S, Colonna M, Kober DL, et al. TREM-2 promotes macrophage survival and lung disease after respiratory viral infection. J Exp Med. 2015;212:681–97.

CAS  PubMed  PubMed Central  Google Scholar 

Zhu Z, Zhang X, Dong W, Wang X, He S, Zhang H, Wang X, Wei R, Chen Y, Liu X, Guo C. TREM2 suppresses the proinflammatory response to facilitate PRRSV infection via PI3K/NF-kappaB signaling. PLoS Pathog. 2020;16:e1008543.

CAS  PubMed  PubMed Central  Google Scholar 

Iizasa E, Chuma Y, Uematsu T, Kubota M, Kawaguchi H, Umemura M, Toyonaga K, Kiyohara H, Yano I, Colonna M, et al. TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation. Nat Commun. 2021;12:2299.

CAS  PubMed  PubMed Central  Google Scholar 

Kosack L, Gawish R, Lercher A, Vilagos B, Hladik A, Lakovits K, Bhattacharya A, Schliehe C, Mesteri I, Knapp S, Bergthaler A. The lipid-sensor TREM2 aggravates disease in a model of LCMV-induced hepatitis. Sci Rep. 2017;7:11289.

PubMed  PubMed Central  Google Scholar 

Qu W, Wang Y, Wu Y, Liu Y, Chen K, Liu X, Zou Z, Huang X, Wu M. Triggering receptors expressed on myeloid cells 2 promotes corneal resistance against pseudomonas aeruginosa by inhibiting caspase-1-dependent pyroptosis. Front Immunol. 2018;9:1121.

PubMed  PubMed Central  Google Scholar 

Sharif O, Gawish R, Warszawska JM, Martins R, Lakovits K, Hladik A, Doninger B, Brunner J, Korosec A, Schwarzenbacher RE, et al. The triggering receptor expressed on myeloid cells 2 inhibits complement component 1q effector mechanisms and exerts detrimental effects during pneumococcal pneumonia. PLoS Pathog. 2014;10:e1004167.

PubMed  PubMed Central  Google Scholar 

Zhu M, Li D, Wu Y, Huang X, Wu M. TREM-2 promotes macrophage-mediated eradication of Pseudomonas aeruginosa via a PI3K/Akt pathway. Scand J Immunol. 2014;79:187–96.

CAS  PubMed  Google Scholar 

Bergmann CC, Lane TE, Stohlman SA. Coronavirus infection of the central nervous system: host-virus stand-off. Nat Rev Microbiol. 2006;4:121–32.

CAS  PubMed  PubMed Central  Google Scholar 

Bergmann CC, Parra B, Hinton DR, Ramakrishna C, Dowdell KC, Stohlman SA. Perforin and gamma interferon-mediated control of coronavirus central nervous system infection by CD8 T cells in the absence of CD4 T cells. J Virol. 2004;78:1739–50.

CAS  PubMed  PubMed Central  Google Scholar 

Wang FI, Stohlman SA, Fleming JO. Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. J Neuroimmunol. 1990;30:31–41.

CAS  PubMed  PubMed Central  Google Scholar 

Savarin C, Dutta R, Bergmann CC. Distinct gene profiles of bone marrow-derived macrophages and microglia during neurotropic coronavirus-induced demyelination. Front Immunol. 2018;9:1325.

PubMed  PubMed Central  Google Scholar 

Xue S, Sun N, Van Rooijen N, Perlman S. Depletion of blood-borne macrophages does not reduce demyelination in mice infected with a neurotropic coronavirus. J Virol. 1999;73:6327–34.

CAS  PubMed  PubMed Central  Google Scholar 

Sariol A, Mackin S, Allred MG, Ma C, Zhou Y, Zhang Q, Zou X, Abrahante JE, Meyerholz DK, Perlman S. Microglia depletion exacerbates demyelination and impairs remyelination in a neurotropic coronavirus infection. Proc Natl Acad Sci USA. 2020;117:24464–74.

CAS  PubMed  PubMed Central  Google Scholar 

Kim TS, Perlman S. Viral expression of CCL2 is sufficient to induce demyelination in RAG1-/- mice infected with a neurotropic coronavirus. J Virol. 2005;79:7113–20.

CAS  PubMed  PubMed Central  Google Scholar 

Jay TR, Miller CM, Cheng PJ, Graham LC, Bemiller S, Broihier ML, Xu G, Margevicius D, Karlo JC, Sousa GL, et al. TREM2 deficiency eliminates TREM2+ inflammatory macrophages and ameliorates pathology in Alzheimer’s disease mouse models. J Exp Med. 2015;212:287–95.

CAS  PubMed  PubMed Central  Google Scholar 

Fleming JO, Trousdale MD, El-Zaatari FA, Stohlman SA, Weiner LP. Pathogenicity of antigenic variants of murine coronavirus JHM selected with monoclonal antibodies. J Virol. 1986;58:869–75.

CAS  PubMed  PubMed Central  Google Scholar 

Hwang M, Phares TW, Hinton DR, Stohlman SA, Bergmann CC, Min B. Distinct CD4 T-cell effects on primary versus recall CD8 T-cell responses during viral encephalomyelitis. Immunology. 2015;144:374–86.

CAS  PubMed  PubMed Central  Google Scholar 

Bergmann CC, Altman JD, Hinton D, Stohlman SA. Inverted immunodominance and impaired cytolytic function of CD8+ T cells during viral persistence in the central nervous system. J Immunol. 1999;163:3379–87.

CAS  PubMed  Google Scholar 

Chen EY, Tan CM, Kou Y, Duan Q, Wang Z, Meirelles GV, Clark NR, Ma’ayan A. Enrichr: interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform. 2013;14:128.

Google Scholar 

Franzen O, Gan LM, Bjorkegren JLM. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database (Oxford). 2019;2019.

Liberzon A, Birger C, Thorvaldsdottir H, Ghandi M, Mesirov JP, Tamayo P. The Molecular Signatures Database (MSigDB) hallmark gene set collection. Cell Syst. 2015;1:417–25.

CAS  PubMed  PubMed Central  Google Scholar 

Butchi NB, Hinton DR, Stohlman SA, Kapil P, Fensterl V, Sen GC, Bergmann CC. Ifit2 deficiency results in uncontrolled neurotropic coronavirus replication and enhanced encephalitis via impaired alpha/beta interferon induction in macrophages. J Virol. 2014;88:1051–64.

PubMed  PubMed Central  Google Scholar 

Savarin C, Stohlman SA, Atkinson R, Ransohoff RM, Bergmann CC. Monocytes regulate T cell migration through the glia limitans during acute viral encephalitis. J Virol. 2010;84:4878–88.

CAS  PubMed  PubMed Central  Google Scholar 

Puntambekar SS, Hinton DR, Yin X, Savarin C, Bergmann CC, Trapp BD, Stohlman SA. Interleukin-10 is a critical regulator of white matter lesion containment following viral induced demyelination. Glia. 2015;63:2106–20.

PubMed  PubMed Central  Google Scholar 

Filipello F, Goldsbury C, You SF, Locca A, Karch CM, Piccio L. Soluble TREM2: innocent bystander or active player in neurological diseases? Neurobiol Dis. 2022;165:105630.

CAS  PubMed  Google Scholar 

Zhong L, Xu Y, Zhuo R, Wang T, Wang K, Huang R, Wang D, Gao Y, Zhu Y, Sheng X, et al. Soluble TREM2 ameliorates pathological phenotypes by modulating microglial functions in an Alzheimer’s disease model. Nat Commun. 2019;10:1365.

PubMed  PubMed Central  Google Scholar 

Bennett ML, Bennett FC, Liddelow SA, Ajami B, Zamanian JL, Fernhoff NB, Mulinyawe SB, Bohlen CJ, Adil A, Tucker A, et al. New tools for studying microglia in the mouse and human CNS. Proc Natl Acad Sci USA. 2016;113:E1738-1746.

CAS  PubMed  PubMed Central  Google Scholar 

Satoh J, Kino Y, Asahina N, Takitani M, Miyoshi J, Ishida T, Saito Y. TMEM119 marks a subset of microglia in the human brain. Neuropathology. 2016;36:39–49.

CAS  PubMed  Google Scholar 

Lier J, Streit WJ, Bechmann I. Beyond activation: characterizing microglial functional phenotypes. Cells. 2021;10:2236.

CAS  PubMed