TDM

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Mincle Agonist - Trehalose-6,6-dimycolate
TDM

Trehalose-6,6-dimycolate (TDM, also known as cord factor) is a unique glycolipid found in the cell wall of Mycobacterium tuberculosis. It is the most abundant lipid found in these bacteria and its presence is believed to correlate with the virulence of tuberculosis. Consequently, it is the most studied immunostimulatory component of M. tuberculosis [1].

Two C-type lectin receptors, macrophage-inducible C-type lectin (Mincle) and macrophage C-type lectin (MCL; also known as Dectin-3), are required for TDM-mediated immune responses [2].

TDM is recognized through its carbohydrate moiety by Mincle and through its lipid tail by MCL [2]. These two receptors form a heterodimer and pair with the signaling adaptor molecule Fc receptor common γ-chain (FcRγ) which in turn recruits spleen tyrosine kinase (Syk) triggering CARD9-Bcl10-MALT1 signaling. Induction of this pathway leads to NF-kB activation and production of a large number of inflammatory cytokines [3,4].

Notably, as TDM orients the maturation of T-helper (Th) cells toward Th1 and Th17 subsets [4], this product is indicated for studying Th1/Th17-polarized immune responses in cellular assays with antigen-presenting cells (APCs).

References:

  1. Ishikawa, E. et al., 2009. Direct recognition of the mycobacterial glycolipid, trehalose dimycolate, by C-type lectin Mincle. J. Exp. Med. 206, 2879–2888.
  2. Richardson MB. & Williams SJK., 2014. MCL and Mincle: C-Type Lectin Receptors That Sense Damaged Self and Pathogen-Associated Molecular Patterns. Front Immunol. 5:288;
  3. Miyake Y. et al., 2015. C-Type Lectin Receptor MCL Facilitates Mincle Expression and Signaling through Complex Formation. J Immunol. 194(11):5366-74.
  4. Geijtenbeek TB. & Gringhuis SI., 2016. C-type lectin receptors in the control of T helper cell differentiation. Nat. Rev. Immunol. 16(7):433-48.

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