FIGURE 2.

Lipopolysaccharide (LPS)‐toll‐like receptor 4 (TLR4) signaling. Lipopolysaccharide is recognized by the complex of toll‐like receptor 4, cluster of differentiation 14 (CD14), and myeloid differentiation 2 (MD‐2). Toll‐like receptor 4 activation leads to the recruitment of additional effector proteins, including myeloid differentiation primary response protein 88 (MYD88), toll/interleukin‐1 receptor domain‐containing adapter protein (TIRAP), toll/interleukin‐1 domain‐containing adaptor protein inducing interferon‐beta‐related adaptor molecule (TRAM), and toll/interleukin‐1 domain‐containing adaptor protein inducing interferon‐beta (TRIF). These further trigger a cascade enabling nuclear factor‐κB (NF‐κB) and interferon regulatory factor 3 (IRF3) to diffuse into the nucleus and to activate the transcription of cytokines, especially tumor necrosis factor alpha, interleukin‐1beta, interleukin‐6, and interleukin‐8, and interferons, aiming at eliminating pathogens. In the circulation, lipopolysaccharide is transported by lipopolysaccharide binding protein (LBP), phospholipid transfer protein (PLTP), and by lipoproteins. Under standard physiologic conditions, lipopolysaccharide preferentially associates with high‐density lipoprotein (HDL), which contributes to its clearance via the liver and bile