Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages invitro and adjuvant activity invivo
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages invitro and adjuvant activity invivo. / Huber, Alexandra; Kallerup, Rie S.; Korsholm, Karen S.; Franzyk, Henrik; Lepenies, Bernd; Christensen, Dennis; Foged, Camilla; Lang, Roland.
In: Innate Immunity, Vol. 22, No. 6, 08.2016, p. 405-418.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Trehalose diester glycolipids are superior to the monoesters in binding to Mincle, activation of macrophages invitro and adjuvant activity invivo
AU - Huber, Alexandra
AU - Kallerup, Rie S.
AU - Korsholm, Karen S.
AU - Franzyk, Henrik
AU - Lepenies, Bernd
AU - Christensen, Dennis
AU - Foged, Camilla
AU - Lang, Roland
PY - 2016/8
Y1 - 2016/8
N2 - The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle.
AB - The T-cell adjuvanticity of mycobacterial cord factor trehalose 6,6'-dimycolate (TDM) is well established. The identification of the C-type lectin Mincle on innate immune cells as the receptor for TDM and its synthetic analogue trehalose 6,6'-dibehenate (TDB) has raised interest in development of synthetic Mincle ligands as novel adjuvants. Trehalose mono- (TMXs) and diesters (TDXs) with symmetrically shortened acyl chains [denoted by X: arachidate (A), stearate (S), palmitate (P), and myristate (M)] were tested. Upon stimulation of murine macrophages, G-CSF secretion and NO production were strongly augmented by all TDXs tested, in a wide concentration range. In contrast, the TMXs triggered macrophage activation only at high concentrations. Macrophage activation by all TDXs required Mincle, but was independent of MyD88. The superior capacity of TDXs for activating macrophages was paralleled by direct binding of TDXs, but not of TMXs, to a Mincle-Fc fusion protein. Insertion of a short polyethylene glycol between the sugar and acyl chain in TDS reduced Mincle-binding and macrophage activation. Immunization of mice with cationic liposomes containing the analogues demonstrated the superior adjuvant activity of trehalose diesters. Overall, immune activation in vitro and in vivo by trehalose esters of simple fatty acids requires two acyl chains of length and involves Mincle.
KW - Vaccine adjuvant
KW - C-type lectin receptor
KW - Mincle
KW - trehalose dimycolate
U2 - 10.1177/1753425916651132
DO - 10.1177/1753425916651132
M3 - Journal article
C2 - 27252171
VL - 22
SP - 405
EP - 418
JO - Innate Immunity
JF - Innate Immunity
SN - 1753-4259
IS - 6
ER -
ID: 173317141