Changes in pro inflammatory and regulatory immune responses during controlled human schistosome infection and the development of clinical symptoms

Abstract

AbstractSchistosomiasis is a prevalent helminthiasis, affecting over 230 million people worldwide, with varied, stage specific morbidity. Whilst the Th2 and regulatory immune responses in chronic infection have been relatively well studied, we have little understanding of human immune responses during acute infection. This is despite the initial infective stages being proposed as crucial targets for much-needed vaccine development. Here, we comprehensively map immune responses in male and female single-sex controlled humanSchistosoma mansoniinfection. Using unbiased, high dimensional techniques we show that human immune responses to male and female single-sex infection are comparable. An early Th1-biased inflammatory response was observed at week 4 post infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. This included expansion of HLA-DR+effector memory T cells, CD38+monocytes and an increase in serum IFNγ. By week 8 post infection these inflammatory responses were followed by an expansion of Th2 and of regulatory cell subsets, including IL-10 producing CD4-CD8-T cells, CD11c+atypical memory B cells and serum IL-10. This study provides immunological insight into the clinical manifestations of acute schistosomiasis, as well as critical context through which to understand the development of immune responses observed in natural infection.One sentence summaryControlled human schistosome infection reveals cellular and cytokine responses to schistosome infection, with early inflammatory responses in symptomatic individuals at week 4 and a balanced Th1, Th2 and regulatory response in all participants by week 8.