@article{31167,
  keywords = {leprosy, TLR4, TRIF, iNOS, Macrophages, Mycobacteria, Phenolic glycolipids},
  author = {Oldenburg R and Mayau V and Prandi J and Arbues A and Astarie-Dequeker C and Guilhot C and Werts C and Winter N and Demangel C},
  title = {Mycobacterial Phenolic Glycolipids Selectively Disable TRIF-Dependent TLR4 Signaling in Macrophages.},
  abstract = {<p>Phenolic glycolipids (PGLs) are cell wall components of a subset of pathogenic mycobacteria, with immunomodulatory properties. Here, we show that in addition, PGLs exert antibactericidal activity by limiting the production of nitric oxide synthase (iNOS) in mycobacteria-infected macrophages. PGL-mediated downregulation of iNOS was complement receptor 3-dependent and comparably induced by bacterial and purified PGLs. Using Mycobacterium leprae PGL-1 as a model, we found that PGLs dampen the toll-like receptor (TLR)4 signaling pathway, with macrophage exposure to PGLs leading to significant reduction in TIR-domain-containing adapter-inducing interferon-β (TRIF) protein level. PGL-driven decrease in TRIF operated posttranscriptionally and independently of Src-family tyrosine kinases, lysosomal and proteasomal degradation. It resulted in the defective production of TRIF-dependent IFN-β and CXCL10 in TLR4-stimulated macrophages, in addition to iNOS. Our results unravel a mechanism by which PGLs hijack both the bactericidal and inflammatory responses of host macrophages. Moreover, they identify TRIF as a critical node in the crosstalk between CR3 and TLR4.</p>
},
  year = {2018},
  journal = {Frontiers in immunology},
  volume = {9},
  pages = {2},
  issn = {1664-3224},
  url = {https://www.frontiersin.org/articles/10.3389/fimmu.2018.00002/pdf},
  doi = {10.3389/fimmu.2018.00002},
  language = {eng},
}