Dynamic Immune Modulation in Fasciolosis: From Protective to Permissive Responses

• Early Th1 response kills NEJs in the peritoneum, lasts up to one week. • Flukes shift response to Th2 to survive, and reduce immune damage in liver. • Fasciolosis Th1-to-Th2 shift mirrors Schistosoma, Taenia , and Ascaris infections. • Vaccines should target early stages of infection before parasites reach the liver. • Several NEJ antigens trigger protective Th1 cytokines, such as IFNγ. This review examines the evolution of the host immune response throughout Fasciola hepatica and Fasciola gigantica infection (fasciolosis). Newly Excysted Juveniles (NEJ) migrate to the peritoneum, where they transiently trigger a protective Th1 immune response that clears most parasites within approximately one week. The remaining flukes penetrate the hepatic parenchyma and initiate a non-protective Th2 immune response. This response promotes parasite survival and reduces hepatic damage by preventing excessive immune damage and inducing rapid fibrous tissue repair. Finally, a mixed regulatory T-cell (Treg)/Th2 response is induced in the last biliary phase. This switch from an initial Th1 immune response to a Th2 one in fasciolosis is comparable to the previously described response against Schistosoma, and this pattern is also found in Echinococcus, Taenia and Ascaris. Hence, an effective vaccine for fasciolosis should be directed towards the early stages of infection when parasites are more vulnerable to immune attack before a functional “point of no return” at which a Th2/Treg response becomes difficult to reverse. This approach could open a new field in vaccine design for other helminthiases.