About this Research Topic
The blood delivered to the liver by the portal vein is critical for the pathophysiology of the organ. About 80% of the blood that percolates the liver is low in oxygen and rich in dietary components and molecules from the commensal microbiota, such as LPS. Although highly immunogenic in the periphery, bacterial and fungal components are tolerated in the liver. Likewise, tumor cells are usually not recognized as immunogenic in the organ, while stromal damage and pathogenic infections may not trigger a conventional robust immune response. The cellular pathways responsible for maintaining this hepatic tolerance are frequently studied and described in the literature. However, what structures are recognized in the liver as immunological danger and how the natural tolerance is broken remains largely unknown. This is a critical aspect of the delicate balance between hepatic tolerance and immunity, significantly impacting human health.
This Research Topic comprises reviews and original research papers aiming to be a forum for experts' ideas regarding liver danger recognition and how tolerance can be overcome. Considering the conventional immune response, Pattern Recognition Receptors (PRR) bind to Pathogen-Associated Molecular Pattern (PAMP) and Damage-Associated Molecular Pattern (DAMPs) molecules and trigger inflammatory responses. The concept of immunological danger is subverted in the hepatic environment, filled with symbiotic bacterial and fungal components from the intestines. In the liver, most cells express immune suppressor receptors, such as PD-1/PD-L1, LSECtin, CTLA4, and Fas-L, and the hepatic stroma is rich in immune downregulatory cytokines, making it primarily tolerogenic. This tendency to tolerance compromises immune competent liver cells in recognizing pathogenic signals and fighting cancer and pathogen-infected cells, for example hepatocytes infected by malaria parasites. The current understanding of intercellular interactions underlining hepatic immunological tolerance will also be approached.
Subtopics may include, but are not limited to:
• Reviews of high-quality literature regarding the hepatic immunological tolerance.
• Mechanisms of hepatocellular carcinoma immune evasion.
• Chronic viral and parasite infections in the liver.
• Cancer stem cell differentiation and survival in the liver.
• T lymphocyte activation in the liver.
• Properties of hepatic antigen-presenting cells.
Keywords: Liver, immune response, immunological danger, cancer, infection
Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.