Identification of an Endogenous Trigger for TLR4 that can trigger Metaflammation
Joint Research Seminar
|Date and Time||11/10/2022 ( Thr. ) 16:30 ~ 18:00|
|Venue||Bldg.1 2F 2-3 conference room|
|Affiliation/Position||Institute of Innate Immunity, University Hospital Bonn, University of Bonn Professor|
|Title||Identification of an Endogenous Trigger for TLR4 that can trigger Metaflammation|
Chronic low-grade inflammation is a hallmark of many non-communicable metabolic diseases such as atherosclerosis or type II diabetes. This so-called metaflammation may, in part, be driven by activation of the innate immune receptor TLR4. Although TLR4 activation is commonly associated with the prototypical agonist bacterial lipopolysaccharide, signaling can also be elicited by host-derived molecules. Whilst many endogenous molecules have been described to activate TLR4, structural studies that support a direct binding to TLR4 and its co-receptor MD-2 are limited. Here we identify the naturally occurring lipid as a novel agonist for the TLR4/MD-2 complex. We provide evidence for a direct interaction between this inducible lipid and TLR4/MD-2, and a potent activation of downstream inflammatory signaling. Our data further reveals elevated concentrations of this lipid in humans in context of excess nutrition and obesity. These findings support the prevailing concept that TLR4 activation by endogenous molecules can fuel obesity-induced metaflammation.