Innate and adaptive immune responses following PD‐L1 blockade in treating chronic murine alveolar echinococcosis

Abstract

Alveolar echinococcosis (AE) is one of the clinically most severe zoonotic helminthic diseases in humans, caused by the continuous proliferation of the larval stage (metacestode) of Echinococcus multilocularis. Upon ingestion of the E. multilocularis eggs by intermediate hosts such as small rodents and human, echinococcal metacestodes form alveolar structures with multiple vesicles of

Impact on Bile Acid Concentrations by Alveolar Echinococcosis and Treatment with Albendazole in Mice

“…Additionally, the present work showed that ABZ treatment ameliorates E. multilocularis infection and almost completely reverses the effects on serum bile acids and gene expression. This further demonstrates the efficacy of ABZ, mainly due to inhibition of parasite proliferation and immune cell infiltration as reported previously [27]. ABZ treatment itself tended to decrease hepatic bile acid concentrations.…”

“…In this model, the parasite mostly grows in the peritoneal cavity. A macroscopic and histological assessment in an earlier study [ 27 ] thus did not detect any visible parasitic structures within the livers of any mouse, but inflammatory cell infiltrates with elevated levels of pro-inflammatory cytokines were observed in infected mice. Furthermore, the treatment efficacy of ABZ was demonstrated in the previous study by a significantly reduced parasite weight (isolated from the peritoneal cavity), the histopathology (immune cell infiltration), and reduced liver tissue cytokine levels.…”

“…In the present investigation, we analyzed serum and liver tissue samples from a previous study on innate and adaptive immune responses in mice infected i.p. with metacestodes of E. multilocularis and treated with vehicle or ABZ [ 27 ]. The natural mode of infection (or primary infection) of intermediate hosts with E. multilocularis represents peroral uptake of infectious eggs, which also includes the first phase of intrahepatic parasite development.…”

“…application of metacestodes of E. multilocularis to mice. While this model does not show macroscopic changes in livers of infected animals, a diffuse infiltration of immune cells in livers and elevated pro-inflammatory cytokines in the plasma of treated animals is found [ 27 ]. Hence, while the animal model does not reproduce completely, the human pathology of AE infection and an oral infection model would more accurately represent it.…”

“…The ratio of total unconjugated to total taurine-conjugated metabolites as well as that of TCA/CA and TβMCA/βMCA in serum are proposed as useful markers to detect the effect of AE and monitor the efficacy of ABZ treatment in the murine chronic infection model applied. It needs to be noted that in this model of secondary infection, histological analysis did not show any macroscopic changes in the liver, but infiltration of immune cells and elevated pro-inflammatory cytokines were observed [ 27 ].…”