Early symptom-associated inflammatory responses shift to type 2 responses in controlled human schistosome infection

Schistosomiasis is an infection caused by contact with Schistosoma-contaminated water and affects more than 230 million people worldwide with varying morbidity. The roles of T helper 2 (T_H2) cells and regulatory immune responses in chronic infection are well documented, but less is known about human immune responses during acute infection. Here, we comprehensively map immune responses during controlled human Schistosoma mansoni infection using male or female cercariae. Immune responses to male or female parasite single-sex infection were comparable. An early T_H1-biased inflammatory response was observed at week 4 after infection, which was particularly apparent in individuals experiencing symptoms of acute schistosomiasis. By week 8 after infection, inflammatory responses were followed by an expansion of T_H2 and regulatory cell subsets. This study demonstrates the shift from T_H1 to both T_H2 and regulatory responses, typical of chronic schistosomiasis, in the absence of egg production and provides immunological insight into the clinical manifestations of acute schistosomiasis.