Enhanced neutrophil functions during Opisthorchis viverrini infections and correlation with advanced periductal fibrosis.

Millions of people are infected with the liver fluke, Opisthorchis viverrini (OV), but only ∼25% of those infected develop liver disease and even fewer develop cholangiocarcinoma. The reasons for these differential outcomes following infection are unknown but it has been proposed that differential immune responses to the parasite may play a role. We therefore measured granulocyte (neutrophil) function in OV-infected individuals, with and without advanced periductal fibrosis (APF), to determine if these cells have a "pro-inflammatory" phenotype that may contribute to liver disease post-infection. A case-controlled study (n=54 in each cohort) from endemic OV-infected areas of northeastern Thailand measured neutrophil functions in whole blood from non-infected (healthy controls) and OV-infected individuals with and without APF. We measured reactive oxygen species (ROS) production, phagocytosis, receptor expression and apoptosis. Secreted products from OV cultures (obtained after in vitro culture of parasites) stimulated ROS production in non-infected healthy controls, but levels were two-fold greater after OV infection (P<0.0001); neutrophil ROS production in individuals with APF was double that observed in those without APF (P<0.0001). OV-infected neutrophils had elevated CD11b expression and greater phagocytic capacity, which was even three-fold higher in those with APF (P