A secreted schistosome cathepsin B1 cysteine protease and acute schistosome infection induce a transient T helper 17 response

The natural history of schistosome infection in the mammalian host is determined by CD4 ⁺ T helper responses mounted against different parasite life cycle stages. A T helper 2 (T _H 2) response to schistosome eggs is required for host survival and establishment of chronic infection. However, a T _H 2 cell-derived cytokine also contributes to an immune milieu that is conducive to schistosome growth and development. Thus, the same responses that allow for host survival have been co-opted by schistosomes to facilitate parasite development and transmission, underscoring the significance of CD4 ⁺ T cell responses to both worms and eggs in the natural history of schistosome infection. Here we show that a cathepsin B1 cysteine protease secreted by schistosome worms not only induces T _H 2 responses, but also T _H 1 and T _H 17 responses, by a mechanism that is dependent on the proteolytic activity of the enzyme. Further investigation revealed that, in addition to the expected T _H 1 and T _H 2 responses, acute schistosome infection also induces a transient T _H 17 response that is rapidly down-regulated at the onset of oviposition. T _H 17 responses are implicated in the development of severe egg-induced pathology. The regulation of worm-induced T _H 17 responses during acute infection could therefore influence the expression of high and low pathology states as infection progresses.