Immune Response to Opisthorchis viverrini Infection and Its Role in Pathology

Human liver fluke infection caused by Opisthorchis viverrini is a major public health problem in Mekong countries such as Thailand, Laos, Cambodia, Vietnam, and Myanmar with over 10 million infected through consumption of fish containing infective metacercariae. With no tissue migration phase and living entirely within the larger secondary (intrahepatic) bile ducts, liver flukes are only exposed to a biliary mucosal immune response, while their excretory and secretory products also stimulate chronic inflammation of biliary epithelium. Neither mucosal nor tissue immune responses appear to cause parasite death or protect against newly established flukes, as evidenced by the persistence of infection for decades in the body and rapid reinfection following treatment. Experimental studies suggest that specific immune suppressive mechanisms may promote parasite persistence, therefore allowing continued secretion of parasite products that damage the biliary epithelium, both directly through mechanical damage and mitogenicity and through innate and adaptive inflammatory responses. Chronic infection is associated with several hepatobiliary diseases, specifically gallbladder and bile duct inflammation (cholecystitis and cholangitis), periductal fibrosis, and cholangiocarcinoma, the fatal bile duct cancer. Various studies have linked the chronic immune response to parasite antigens to both fibrosis and many steps in the carcinogenic process. Here, we review research-based understandings of the basic immune response to liver fluke infection and its roles in host protection and immunopathogenesis from available literature and also from recent studies conducted by the authors.