Furfurman - Dectin-2 Agonist

Dectin-2 agonist - Malassezia furfur cell wall preparation

Furfurman is a cell wall preparation of Malassezia furfur extracted using a mixture of chloroform and methanol.

Malassezia furfur is an opportunistic skin fungal pathogen that is recognized by the C-type lectin receptors, in particular Dectin-2 [1].

This receptor plays an important role in antifungal innate immunity. Dectin-2 binds to mannose carbohydrates, such as the mannose-capped lipoarabinomannan of mycobacteria [2] and α-mannans found in Candida albicans [3].

Upon binding to its ligand, Dectin-2 couples with the Fc receptor gamma chain [4] and signals through the kinase Syk and the adaptors CARD9/Bcl-10/MALT1, triggering the activation of NF-κB and the subsequent production of pro-inflammatory cytokines [5].

Furfurman selectively activates Dectin-2, although at high concentrations it can also activate Dectin-1.

Indeed, activation of Dectin-2 by furfurman depends on the presence of terminal a-mannose caps in the latter, as demonstrated by treatment of furfurman with an exo-α-mannosidase, an enzyme that removes mannose groups.

References:

1. Ishikawa T. et al., 2013. Identification of distinct ligands for the C-type lectin receptors Mincle and Dectin-2 in the pathogenic fungus Malassezia. Cell Host Microbe. 13(4):477-88.
2. Yonekawa A. et al., 2014. Dectin-2 is a direct receptor for mannose‑capped lipoarabinomannan of mycobacteria. Immunity. 41(3):402-13.
3. Saijo S. et al., 2010. Dectin-2 recognition of alpha-mannans and induction of Th17 cell differentiation is essential for host defense against Candida albicans. Immunity. 32(5):681-91.
4. Sato K. et al., 2006. Dectin-2 is a pattern recognition receptor for fungi that couples with the Fc receptor gamma chain to induce innate immune responses. J Biol Chem. 281(50):38854-66.
5. Sancho D. & Reis e Sousa C., 2012. Signaling by myeloid C-type lectin receptors in immunity and homeostasis. Annu Rev Immunol. 30:491-529.