Abstract
Infection with the intravascular diecious trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world, affecting over 258 million people worldwide. During chronic Schistosoma mansoni infection, complex immune responses to tissue-entrapped parasite eggs provoke granulomatous inflammation which leads to serious damage of the liver and intestine. The suppression of protective host immune mechanisms by helminths promotes parasite survival and benefits the host by reducing tissue damage. However, immune-suppressive cytokines may reduce vaccine-induced immune responses. By combining a single-sex infection system with a murine air pouch model, we were able to demonstrate that male and female schistosomes play opposing roles in modulating the host’s immune response. Female schistosomes suppress early innate immune responses to invading cercariae in the skin and upregulate anergy-associated genes. In contrast, male schistosomes trigger strong innate immune reactions which lead to a reduction in worm and egg burden in the liver. Our data suggest that the female worm is a neglected player in the dampening of the host’s immune defense system and is therefore a promising target for new immune modulatory therapies.
Highlights
Infection with the intravascular trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world
To investigate whether the sex of adult S. mansoni living in the intestine impacts the early dermal immune defense reaction to invading cercariae, cercariae were injected into air pouches in mice carrying adult female worms, adult male worms, or worm pairs
We demonstrate that male and female schistosomes play different roles in modulating the host’s immune response
Summary
Infection with the intravascular trematode Schistosoma spp. remains a serious tropical disease and public health problem in the developing world. Schistosoma mansoni, which causes intes tinal schistosomiasis, accounts for around 80 million infections in Africa, the Near East and South America [4]. The host’s immune system is faced with different developmental stages of the parasite, from skin-penetrating cercarial larvae, juveniles which pass through the heart and lungs, Schistosoma Sex Determines Immune Responses and egg-producing adult worm pairs which inhabit the mesenteric vasculature. The adults produce up to 300 tissuedamaging eggs per day [5]. Most of the eggs are flushed into the liver where they become entrapped within the hepatic sinusoids and provoke a sustained inflammatory-driven process. The accumulating eggs cause pronounced intestinal and hepatic fibrosis, which in turn leads to portal hypertension and its sequels—including variceal bleeding and ascites [6, 7]
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