Introduction
Intestinal barrier
Physical barrier
Immune barrier
Location | Cell type | Function | Refs. |
---|---|---|---|
Mucous layer | Intestinal macrophages | Phagocytosis and degradation of microorganisms and dead tissue cells Producing mediators that drive epithelial cell renewal | [33] |
Dendritic cells | Having the ability to open TJs between epithelial cells and directly take up luminal microorganisms | [36] | |
Local interepithelial lymphocytes: conventional and nonconventional TCRαβ+ subsets; TCRγδ+ subgroups | Guarding the intestinal epithelial barrier Rapidly activating cytolytic and Th1-cell cytokine responses aimed at an infected or stressed epithelium | ||
ILC1 | Being activated by myeloid-cell-derived IL-12 | ||
ILC2 | Being activated by epithelial-derived cytokines and orchestrate type 2 immunity | ||
ILC3 | Interacting with cells of both the innate and adaptive immune systems Secreting IL-22 and initiating an antimicrobial program as well as barrier fortification in epithelial cells | ||
Intestinal B cells | Producing the SIgA | [40] | |
Invariant T cells: MAIT cells | Rapidly producing cytokines and exerting cytolytic activity after activation by cells infected with bacteria, including several enteric species | [34] | |
iNKT cells | Producing large amounts of IL-4 and IFN-γ involved in the immune response | [34] | |
Mucous layer and submucosa | Lymphatic follicles | Involved in the local immune response, namely through collaboration with epithelium to effectively localize entry of foreign materials to sites where antigens and microorganisms can be immediately endocytosed, processed, and presented for primary or memory immune responses without the need for systemic involvement | [31] |
Commensal microbiota in intestines
The gut–liver axis
The physiological “gut–liver axis”
Immunological defense of the liver
Effects of sepsis on the intestinal barrier and microbiota
The gut–liver axis in sepsis
Specific role of lipopolysaccharides
Effects of gut dysfunction on the liver
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 |