The innate immune response during liver inflammation and metabolic disease

• TLR signaling in liver is important to maintain the inflammatory balance.
• Inflammasome activation has been implicated in several liver diseases.
• Metabolic stress can initiate inflammatory responses in the liver.
• Interplay between immune cells and resident liver cells is crucial during inflammation.

The role of the inflammatory response is to combat tissue injury and infection. Innate immune cells recognize cell damage or pathogen invasion with intracellular or surface-expressed pattern recognition receptors (PRRs). Activated PRRs subsequently initiate signaling cascades that trigger the release of factors promoting the inflammatory response. Because the liver is a site where foreign antigens from the gastrointestinal tract encounter the immune system, it is particularly enriched with innate immune cells. These cells can modify and disrupt critical processes implicated in metabolic disease. As such, metabolic stress initiates a feedforward cycle of inflammatory responses, resulting in a state of unresolved chronic inflammation in the liver. Accordingly, the crosstalk between these innate immune cells and the resident parenchymal cells plays an important role in the development of acute and chronic liver disease.