CD11c depletion impairs the ongoing Th2 response during chronic infection

Schistosomes are parasitic helminths that survive for years in the human host, resulting in chronic antigen exposure and Th2 dominated inflammatory pathology. Dendritic cells have been shown to be both sufficient and necessary to initiate Th2 immune responses against schistosomes and other helminths, but the role CD11c+ cells may play in the maintenance of anti-helminth CD4+ T cell responses has yet to be shown. To test key questions about chronic Th2 response maintenance during schistosome infection, we have used a murine model(CD11c.DOG x IL-4get), which allows inducible depletion of CD11c+ cells with diphtheria toxin (DTx) and also the identification of cells that express IL-4 mRNA. DTx was administered to S. mansoni infected mice between days 42 and 51 of infection and immunology, parasitemia and pathology assessed by multi-colour flow cytometry, ELISA, liver enzyme assays, egg counts and histology. CD11c depletion led to a reduction in the percentage and number of CD4+ T cells in the liver, which is a key effector site in S. mansoni infection. This was associated with a significant decrease in the Th2 response, characterised by the loss of IL-4 mRNA expression and protein production. Surprisingly, these data suggest that CD11c+ cells are important for maintenance of the Th2 response at effector sites during helminth infection, possibly through recruitment, retention or reactivation of CD4+ T cells.