About this Research Topic
Chronic liver inflammation due to infectious and non-infectious diseases drives hepatic fibrosis. The liver is a unique organ with an extraordinary ability to regenerate upon different injuries. However, chronic liver inflammation due to various etiologies, e.g. metabolic and immune disorders, bacterial, parasitic and viral infections results in liver fibrosis, often leading to cirrhosis and carcinogenesis. In both acute and chronic inflammation, a variety of immune and non-immune cells in the liver is involved in the processes resulting in either regeneration or fibrosis.
Chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, TNF-α, and IL-6) are critically involved in infectious diseases, inflammation, steatosis, fibrosis, and cancer development. These cytokines are mainly produced by resident macrophages and, to some extent, also by recruited macrophages and neutrophils. In the pathogenesis of several liver infectious and non-infectious diseases, NLRP3 inflammasome has an essential role in shaping adaptive immune responses in liver fibrosis. On the contrary, the common mediators of organ fibrosis are IL-10 cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), TGF-β, VEGF, EGF, among others. Among all these, TGF-β1 has been identified as the most profibrotic cytokine (in both infectious and non-infectious liver fibrosis), and it stimulates its own production by myofibroblasts, thereby establishing an autocrine cycle of myofibroblast differentiation and activation.
Studies about cells (e.g. hepatic stellate cells, hepatocytes, endothelial cells, infiltrating macrophages) and the molecular mediators (e.g. autophagy regulators, TGF, proinflammatory cytokines) involved in the development of liver fibrosis as well as new therapies are a hot spot in liver pathology research. Although the development of anti-inflammatory, immunosuppressive, and anti-viral therapies could contribute to reducing liver damage by decreasing inflammation, the first step that leads to fibrosis as a mechanism of repair and the elimination of etiological agents, often result insufficient. Therefore, the study of profibrotic mechanisms, will give possibilities to design specific anti-fibrotic interventions. In addition to the development of fibrosis and the consequent damage to the liver host, most of parasitic and bacterial infections take advantage of the induction of fibrosis to generate granulomas. The latter favor the generation of a niche of survival for the pathogen that allows the chronicity of the infection.
This Research Topic will provide advances on liver inflammation and hepatic fibrosis due to infectious diseases and in comparison to non-infectious diseases, including immunopathology, new therapeutic targets and treatments. We welcome the submission of Original Research articles, Reviews, Mini-Reviews, and Perspectives that cover, but are not limited to, the following topics:
(1) Immune responses in the liver during bacterial infection (e.g. Salmonella spp, Brucella spp, Listeria monocytogenes).
(2) Immune responses in the liver during parasitic infection (e.g. Fasciola hepatica, Schistosoma spp, Echinococcus granulosus).
(3) Immune responses in the liver during viral infection (e.g. HBV, HCV, associated or not with HIV).
(4) Comparison of common immune pathways modulated in the liver during infectious vs. non-infectious diseases, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), among others.
Chronic liver diseases are cytokine-driven diseases as several proinflammatory cytokines (IL-1α, IL-1β, TNF-α, and IL-6) are critically involved in infectious diseases, inflammation, steatosis, fibrosis, and cancer development. These cytokines are mainly produced by resident macrophages and, to some extent, also by recruited macrophages and neutrophils. In the pathogenesis of several liver infectious and non-infectious diseases, NLRP3 inflammasome has an essential role in shaping adaptive immune responses in liver fibrosis. On the contrary, the common mediators of organ fibrosis are IL-10 cytokine family members (IL-10, IL-19, IL-20, IL-22, IL-24, and IL-26), TGF-β, VEGF, EGF, among others. Among all these, TGF-β1 has been identified as the most profibrotic cytokine (in both infectious and non-infectious liver fibrosis), and it stimulates its own production by myofibroblasts, thereby establishing an autocrine cycle of myofibroblast differentiation and activation.
Studies about cells (e.g. hepatic stellate cells, hepatocytes, endothelial cells, infiltrating macrophages) and the molecular mediators (e.g. autophagy regulators, TGF, proinflammatory cytokines) involved in the development of liver fibrosis as well as new therapies are a hot spot in liver pathology research. Although the development of anti-inflammatory, immunosuppressive, and anti-viral therapies could contribute to reducing liver damage by decreasing inflammation, the first step that leads to fibrosis as a mechanism of repair and the elimination of etiological agents, often result insufficient. Therefore, the study of profibrotic mechanisms, will give possibilities to design specific anti-fibrotic interventions. In addition to the development of fibrosis and the consequent damage to the liver host, most of parasitic and bacterial infections take advantage of the induction of fibrosis to generate granulomas. The latter favor the generation of a niche of survival for the pathogen that allows the chronicity of the infection.
This Research Topic will provide advances on liver inflammation and hepatic fibrosis due to infectious diseases and in comparison to non-infectious diseases, including immunopathology, new therapeutic targets and treatments. We welcome the submission of Original Research articles, Reviews, Mini-Reviews, and Perspectives that cover, but are not limited to, the following topics:
(1) Immune responses in the liver during bacterial infection (e.g. Salmonella spp, Brucella spp, Listeria monocytogenes).
(2) Immune responses in the liver during parasitic infection (e.g. Fasciola hepatica, Schistosoma spp, Echinococcus granulosus).
(3) Immune responses in the liver during viral infection (e.g. HBV, HCV, associated or not with HIV).
(4) Comparison of common immune pathways modulated in the liver during infectious vs. non-infectious diseases, including alcoholic liver disease, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), among others.
Keywords: Liver Fibrosis, Liver immune response, Bacteria and liver, Parasite and liver, Virus and liver
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