Table 2 Roles of gut-derived PAMPs and DAMPs in the liver after sepsis
From: The gut–liver axis in sepsis: interaction mechanisms and therapeutic potential
Components | Roles | Refs. |
|---|---|---|
LPS | Passing through the intestine to reach the IECs via multiple alternative paths Detoxification of LPS by the liver and LPS-binding proteins in plasma Activation of TLR4 signaling Plasma lipoproteins neutralize LPS and accelerate LPS clearance | |
LSECs | Detecting and capturing pathogens, presenting antigens Contributing to migration of leukocytes to inflammatory sites | |
Macrophages | ||
KCs | Constituting the majority of hepatic macrophages in a healthy liver | |
Macrophage polarization | M1-like macrophages, as triggered by TLR ligands and IFN-γ, produce proinflammatory cytokines (IL-1β, TNF, IL-6, etc.) M2-like macrophages, as activated by IL-4/IL-13, IL-10, IL-1 receptor antagonist, are critical for anti-inflammatory effects and repairing tissue damage | |
Assembly of inflammasomes | NLRP3 and AIM2 inflammasomes cause detrimental inflammation | |
Macrophage autophagy | Alleviating hepatic inflammation | |
KCs-platelet interaction | Platelet recruitment and limiting bacterial infection in sepsis | |
Neutrophils | Migrating to liver sinusoids and releasing NETs to collect and remove bacteria | |
NK cells and NKT cells | Contributing to antibacterial defense | |
Hepatocytes | Hepatocyte dysfunction and abnormal lipid metabolism Alterations of BA metabolism Causing excretory liver dysfunction | |
Vagal nerve | Serving as the primary sensory and efferent nerve in the digestive system; among the organs within the abdominal cavity, the liver is a major target of the vagus nerve Stimulation of the efferent arm of vagal circuits can control release of proinflammatory cytokines and promote immune cell activation and differentiation toward a pro-regenerative phenotype Vagus nerve signaling is a critical component of the cholinergic anti-inflammatory pathway |