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

Kateryna Soloviova, Ellen C. Fox, John P. Dalton, Conor R. Caffrey, Stephen J. Davies*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

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.

Original languageEnglish
Article numbere0007070
JournalPLoS Neglected Tropical Diseases
Volume13
Issue number1
DOIs
StatePublished - 2019
Externally publishedYes

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