Interleukin-13 in the skin and interferon-γ in the liver are key players in immune protection in human schistosomiasis

Immunity against schistosomes includes anti‐infection immunity, which is mainly active against invading larvae in the skin, and anti‐disease immunity, which controls abnormal fibrosis in tissues invaded by schistosome eggs. Anti‐infection immunity is T‐helper 2 (Th2) cell‐dependent and is controlled by a major genetic locus that is located near the Th2 cytokine locus on chromosome 5q31‐q33. Mutations in the gene encoding interleukin (IL)‐13 that decrease or increase IL‐13 production account, at least in part, for that genetic control. In contrast, protection against hepatic fibrosis is dependent on interferon (IFN)‐γ and is controlled by a major genetic locus that is located on 6q23, near the gene encoding the IFN‐γ receptor β chain. Mutations that modulate IFN‐γ gene transcription are associated with different susceptibility to disease. These data indicate that IL‐13 in the skin and IFN‐γ in the liver are key players in protective immunity against schistosomes. These roles relate to the high anti‐fibrogenic activities of IFN‐γ and to the unique ability of IL‐13 in Th2 priming in the skin and in the mobilization of eosinophils in tissues. The coexistence of strong IFN‐γ and IL‐13‐mediated immune responses in the same subject may involve the compartmentalization of the anti‐schistosome immune response between the skin and the liver.