TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation.
Adaptor Proteins, Signal Transducing
/ genetics
Animals
CARD Signaling Adaptor Proteins
/ genetics
Cell Wall
/ metabolism
Cells, Cultured
Disease Models, Animal
Female
Glycolipids
/ metabolism
Humans
Immune Evasion
Latent Tuberculosis
/ immunology
Lectins, C-Type
/ genetics
Macrophage Activation
/ immunology
Macrophages
/ immunology
Male
Membrane Glycoproteins
/ genetics
Membrane Proteins
/ genetics
Mice
Mice, Knockout
Mycobacterium tuberculosis
/ immunology
Mycolic Acids
/ metabolism
Primary Cell Culture
Receptors, IgG
/ metabolism
Receptors, Immunologic
/ genetics
Virulence Factors
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
16 04 2021
16 04 2021
Historique:
received:
22
06
2020
accepted:
17
03
2021
entrez:
17
4
2021
pubmed:
18
4
2021
medline:
4
5
2021
Statut:
epublish
Résumé
Mycobacterial cell-wall glycolipids elicit an anti-mycobacterial immune response via FcRγ-associated C-type lectin receptors, including Mincle, and caspase-recruitment domain family member 9 (CARD9). Additionally, mycobacteria harbor immuno-evasive cell-wall lipids associated with virulence and latency; however, a mechanism of action is unclear. Here, we show that the DAP12-associated triggering receptor expressed on myeloid cells 2 (TREM2) recognizes mycobacterial cell-wall mycolic acid (MA)-containing lipids and suggest a mechanism by which mycobacteria control host immunity via TREM2. Macrophages respond to glycosylated MA-containing lipids in a Mincle/FcRγ/CARD9-dependent manner to produce inflammatory cytokines and recruit inducible nitric oxide synthase (iNOS)-positive mycobactericidal macrophages. Conversely, macrophages respond to non-glycosylated MAs in a TREM2/DAP12-dependent but CARD9-independent manner to recruit iNOS-negative mycobacterium-permissive macrophages. Furthermore, TREM2 deletion enhances Mincle-induced macrophage activation in vitro and inflammation in vivo and accelerates the elimination of mycobacterial infection, suggesting that TREM2-DAP12 signaling counteracts Mincle-FcRγ-CARD9-mediated anti-mycobacterial immunity. Mycobacteria, therefore, harness TREM2 for immune evasion.
Identifiants
pubmed: 33863908
doi: 10.1038/s41467-021-22620-3
pii: 10.1038/s41467-021-22620-3
pmc: PMC8052348
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
CARD Signaling Adaptor Proteins
0
Card9 protein, mouse
0
Clecsf8 protein, mouse
0
Glycolipids
0
Lectins, C-Type
0
Membrane Glycoproteins
0
Membrane Proteins
0
Mycolic Acids
0
Receptors, IgG
0
Receptors, Immunologic
0
Trem2 protein, mouse
0
Tyrobp protein, mouse
0
Virulence Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2299Références
J Res Med Sci. 2018 Jul 26;23:63
pubmed: 30181745
Mucosal Immunol. 2008 May;1(3):229-38
pubmed: 19079182
J Neurochem. 2009 May;109(4):1144-56
pubmed: 19302484
Immunity. 2014 Nov 20;41(5):685-93
pubmed: 25517611
J Immunol. 1999 Mar 15;162(6):3504-11
pubmed: 10092807
Eur J Immunol. 2012 Jan;42(1):176-85
pubmed: 21956652
Cell. 2014 Dec 18;159(7):1497-509
pubmed: 25525872
Immunity. 2017 Sep 19;47(3):552-565.e4
pubmed: 28844797
J Exp Med. 2005 Feb 21;201(4):647-57
pubmed: 15728241
Trends Immunol. 2009 May;30(5):234-42
pubmed: 19359218
Nat Immunol. 2007 Jan;8(1):39-46
pubmed: 17159982
Nat Genet. 2000 Jul;25(3):357-61
pubmed: 10888890
Chem Biol. 2009 Jan 30;16(1):82-92
pubmed: 19171308
J Exp Med. 2009 Jan 16;206(1):89-97
pubmed: 19139169
Nat Rev Microbiol. 2020 Jan;18(1):47-59
pubmed: 31728063
Cell. 2015 Mar 12;160(6):1061-71
pubmed: 25728668
Biochem Biophys Res Commun. 2005 Nov 18;337(2):452-6
pubmed: 16198315
Proc Natl Acad Sci U S A. 1997 May 13;94(10):5243-8
pubmed: 9144222
Immunology. 2003 Aug;109(4):547-51
pubmed: 12871221
PLoS Pathog. 2010 Dec 16;6(12):e1001230
pubmed: 21187903
Nat Immunol. 2007 Jun;8(6):619-29
pubmed: 17486093
J Clin Invest. 1998 Sep 15;102(6):1229-38
pubmed: 9739057
JAMA Neurol. 2014 Apr;71(4):449-53
pubmed: 24535663
Nat Immunol. 2009 Apr;10(4):340-7
pubmed: 19295630
Chem Biol. 2014 Jan 16;21(1):67-85
pubmed: 24374164
Clin Exp Immunol. 2010 Jul 1;161(1):1-9
pubmed: 20491796
Immunity. 2014 Mar 20;40(3):414-24
pubmed: 24631157
PLoS One. 2015 Dec 23;10(12):e0145342
pubmed: 26699615
Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15918-23
pubmed: 14663145
Immunogenetics. 2012 Jan;64(1):39-47
pubmed: 21800138
Front Immunol. 2017 Mar 27;8:303
pubmed: 28396660
J Neurochem. 2009 Jul;110(1):284-94
pubmed: 19457124
Nature. 2004 Sep 2;431(7004):84-7
pubmed: 15343336
J Exp Med. 2004 Dec 20;200(12):1559-69
pubmed: 15611286
Biochem Biophys Res Commun. 2011 Jun 3;409(2):304-7
pubmed: 21575604
Mol Microbiol. 2008 Jul;69(1):164-74
pubmed: 18466296
J Exp Med. 2002 Apr 15;195(8):991-1001
pubmed: 11956290
J Exp Med. 2005 Dec 19;202(12):1649-58
pubmed: 16352737
J Biol Chem. 2014 May 30;289(22):15405-12
pubmed: 24733387
Heliyon. 2020 May 27;6(5):e04064
pubmed: 32490252
Immunity. 2011 May 27;34(5):651-64
pubmed: 21616435
Mucosal Immunol. 2014 May;7(3):670-83
pubmed: 24172845
PLoS Pathog. 2014 Jun 12;10(6):e1004167
pubmed: 24945405
Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3285-E3294
pubmed: 28373578
Front Immunol. 2017 Feb 15;8:84
pubmed: 28261197
J Immunol. 2006 Sep 15;177(6):3520-4
pubmed: 16951310
Immunobiology. 2004;209(1-2):117-27
pubmed: 15481146
PLoS Med. 2007 Apr;4(4):e124
pubmed: 17425404
Blood. 2013 Mar 14;121(11):1951-60
pubmed: 23293083
Curr Opin Immunol. 2009 Feb;21(1):38-46
pubmed: 19230638
Int J Tuberc Lung Dis. 2012 Feb;16(2):150-6
pubmed: 22137597
Proc Natl Acad Sci U S A. 2009 Jan 6;106(1):256-61
pubmed: 19109436
J Biol Chem. 2008 Oct 24;283(43):28835-41
pubmed: 18703502
Nature. 2014 Jan 9;505(7482):218-22
pubmed: 24336213
J Immunol. 2008 Jul 15;181(2):918-30
pubmed: 18606643
Mol Immunol. 2014 Nov;62(1):169-77
pubmed: 25004110
Am J Hum Genet. 2002 Sep;71(3):656-62
pubmed: 12080485
Immunol Rev. 2015 Mar;264(1):182-203
pubmed: 25703560
Elife. 2016 Dec 20;5:
pubmed: 27995897
Infect Immun. 1999 Aug;67(8):4223-30
pubmed: 10417195
N Engl J Med. 2013 Jan 10;368(2):107-16
pubmed: 23150908
Tuberculosis (Edinb). 2019 Mar;115:26-41
pubmed: 30948174
Immun Inflamm Dis. 2016 Aug 24;4(4):401-412
pubmed: 27980775
PLoS One. 2009 Dec 29;4(12):e8459
pubmed: 20041183
J Exp Med. 2001 Oct 15;194(8):1111-22
pubmed: 11602640
Nat Commun. 2016 Apr 18;7:11322
pubmed: 27089465
PLoS One. 2014 Feb 06;9(2):e87329
pubmed: 24516549
Prog Lipid Res. 2012 Oct;51(4):325-39
pubmed: 22659327
Nat Immunol. 2008 Oct;9(10):1179-88
pubmed: 18776906
Immunity. 2013 May 23;38(5):1050-62
pubmed: 23602766
J Immunol. 2007 Sep 15;179(6):4015-26
pubmed: 17785840
Trends Immunol. 2017 Jan;38(1):66-76
pubmed: 27889398
J Clin Invest. 2003 Feb;111(3):323-32
pubmed: 12569157
Infect Immun. 2012 Apr;80(4):1381-9
pubmed: 22290144
N Engl J Med. 2013 Jan 10;368(2):117-27
pubmed: 23150934
Vaccine. 2017 Jun 14;35(27):3433-3440
pubmed: 28476627
J Immunol. 2015 Jun 1;194(11):5366-74
pubmed: 25888641
J Biol Chem. 2010 Jun 4;285(23):17380-9
pubmed: 20375425
Microbiol Immunol. 2001;45(12):801-11
pubmed: 11838897
Tuberculosis (Edinb). 2003;83(1-3):91-7
pubmed: 12758196
J Interferon Cytokine Res. 2009 Jun;29(6):313-26
pubmed: 19441883
Infect Immun. 1986 Dec;54(3):869-75
pubmed: 3781628
Neuron. 2016 Jul 20;91(2):328-40
pubmed: 27477018
J Microbiol. 2013 Oct;51(5):619-26
pubmed: 24037657
J Neurochem. 2004 Nov;91(3):568-78
pubmed: 15485488
J Exp Med. 2009 Dec 21;206(13):2879-88
pubmed: 20008526
Rev Soc Bras Med Trop. 2017 Jan-Feb;50(1):9-18
pubmed: 28327797
J Clin Invest. 2012 Mar;122(3):787-95
pubmed: 22378047
J Immunol. 2003 Jul 15;171(2):594-9
pubmed: 12847223
Pathog Dis. 2014 Mar;70(2):132-40
pubmed: 24190334
Int Immunol. 2001 Oct;13(10):1283-90
pubmed: 11581173
Curr Opin Immunol. 2015 Feb;32:21-7
pubmed: 25553393
Immunity. 2016 Dec 20;45(6):1245-1257
pubmed: 27887882
Immunity. 2014 Sep 18;41(3):402-413
pubmed: 25176311
Cancer Lett. 2000 Oct 31;159(2):189-95
pubmed: 10996731
J Exp Med. 2010 Apr 12;207(4):777-92
pubmed: 20351059
Nat Immunol. 2012 Sep;13(9):817-22
pubmed: 22910394
Proc Natl Acad Sci U S A. 2009 Feb 10;106(6):1897-902
pubmed: 19171887
J Leukoc Biol. 2007 Jan;81(1):272-83
pubmed: 17035338
Immunobiology. 2008;213(9-10):701-13
pubmed: 18926286
Clin Genet. 2013 Jun;83(6):525-6
pubmed: 23347262
Sci Signal. 2010 May 18;3(122):ra38
pubmed: 20484116
Proc Natl Acad Sci U S A. 2001 Jul 3;98(14):7958-63
pubmed: 11438742