A one-year unisexual Schistosoma mansoni infection causes pathologic organ alterations and persistent non-polarized T cell-mediated inflammation in mice

Abstract

In exhibiting gonochorism and phenotypic sexual dimorphism, Schistosoma spp. are unique among trematodes. Only females mating with male schistosomes can produce the highly immunogenic parasite eggs which determine the clinical picture of the disease schistosomiasis. The strong immune-modulatory effect of the eggs masks the influence of the adult worms. To shed light on the complexity of the immune response triggered by adult worms of Schistosoma mansoni, we performed a long-term unisexual infection experiment in mice. We were able to demonstrate that both male and female schistosomes can survive unpaired for one year in the murine host. Furthermore, unisexual S. mansoni infection leads to pronounced inflammation of the liver characterized by a non-polarized Th1/Th2 immune response, regardless of worm sex.

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

“…Throughout infection we have shown only minor differences in immune response between female and male single-sex infection with schistosomes. This finding is in line with the initial immunological analysis we have performed on the separate controlled human infection studies( 3, 5 ), as well as a recent murine study which found no immunological differences in chronic male or female single-sex infection( 48 ). However, it is still surprising in the context of prior papers that have shown sex-related differences in immune priming, as well as the known morphological and transcriptional differences between male and female worms ( 49–52 ).…”

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

“…Throughout infection, we have shown only minor differences in immune response between female and male single-sex infections. This finding is in line with the initial immunological analysis we have performed on the separate controlled human infection studies ( 3 , 5 ) and a recent murine study that found no immunological differences in chronic male or female single-sex infection ( 14 ). However, it is still unexpected in the context of prior papers that have shown sex-related differences in immune priming, as well as the known morphological and transcriptional differences between male and female worms ( 15 – 18 ).…”

“…In murine models, egg production is the major driver of type 2 immune responses in schistosomiasis (10), with a mixed type 1/type 2 response present in prepatent or single-sex S. mansoni infection (11)(12)(13). Schistosome worms exhibit marked morphological and transcriptional differences dependent on sex; however, whether this translates to altered immune phenotypes is unclear (14)(15)(16)(17)(18).…”

Safety and infectivity of female cercariae in Schistosoma-naïve, healthy participants: a controlled human Schistosoma mansoni infection study

“… 17 The similarity between male- and female-induced immune responses is in line with recent work using long-term male and female schistosome infections in a murine model. 18 However, it contrasts prior literature which suggested male-only infections induce a more pro-inflammatory response, whilst female-only infection are characterized by more regulatory profiles. 7 , 19 However, given the very small set of individuals in both our male- and female-only CHI-S studies, more in-depth immunological assessments will be needed to confirm similarity of immune interaction between male and female worms.…”