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TREM2 is a receptor for non-glycosylated mycolic acids of mycobacteria that limits anti-mycobacterial macrophage activation
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)
- Publication Year :
- 2020
-
Abstract
- 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. Download PDF<br />論文
- Subjects :
- 0301 basic medicine
Male
General Physics and Astronomy
Mycolic acid
Mice
0302 clinical medicine
Cell Wall
Macrophage
Receptors, Immunologic
Receptor
Cells, Cultured
chemistry.chemical_classification
Mice, Knockout
Multidisciplinary
Membrane Glycoproteins
Chemistry
Mycolic Acids
lipids (amino acids, peptides, and proteins)
Female
medicine.symptom
Pattern recognition receptors
Virulence Factors
Science
Primary Cell Culture
Inflammation
General Biochemistry, Genetics and Molecular Biology
Article
Microbiology
Proinflammatory cytokine
03 medical and health sciences
Immune system
Glycolipid
Immunity
Latent Tuberculosis
medicine
Animals
Humans
Lectins, C-Type
Monocytes and macrophages
Adaptor Proteins, Signal Transducing
Immune Evasion
Macrophages
Receptors, IgG
Membrane Proteins
General Chemistry
Mycobacterium tuberculosis
Antimicrobial responses
Macrophage Activation
CARD Signaling Adaptor Proteins
Disease Models, Animal
030104 developmental biology
Glycolipids
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Issue :
- 1
- Database :
- OpenAIRE
- Journal :
- Nature communications
- Accession number :
- edsair.doi.dedup.....54b5a03bee45bb34e1ccd2cc29769315