Human serum activates the tegument of female schistosomes and supports recovery from Praziquantel

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IMMUNOLOGY AND HOST-PARASITE INTERACTIONS - ORIGINAL PAPER

Human serum activates the tegument of female schistosomes and supports recovery from Praziquantel Franziska Winkelmann 1 & Marcus Frank 2,3 & Anne Rabes 1 & Nicole Koslowski 1 & Cindy Schulz 1 & Miriam Bischofsberger 1 & Emil C. Reisinger 1 & Martina Sombetzki 1 Received: 3 April 2020 / Accepted: 4 November 2020 # The Author(s) 2020

Abstract Schistosomiasis is one of the most devastating parasitic disease in the world. Schistosoma spp. survive for decades within the vasculature of their human hosts. They have evolved a vast array of mechanisms to avoid the immune reaction of the host. Due to their sexual dimorphism, with the female worm lying within the gynecophoric canal of the male worm, it is the male that is exposed to the immediate environment and the soluble parts of the host’s immune response. To understand how the worms are so successful in fending off the immune attacks of the host, comparative analyses of both worm sexes in human serum (with or without Praziquantel) were performed using scanning electron microscopy, transmission electron microscopy, and immunohistochemistry. Further, gene expression analyses of tegument-specific genes were performed. Following the incubation in human serum, males and females out of pairs show morphological changes such as an altered structure of the pits below the surface and an increased number of pits per area. In addition, female schistosomes presented a marked tuft-like repulsion of their opsonized surface. The observed resistance of females to Praziquantel seemed to depend on active proteins in the human serum. Moreover, different expression profiles of tegument-specific genes indicate different functions of female_single and male_single teguments in response to human serum. Our results indicate that female schistosomes developed different evasion strategies toward the host’s immune system in comparison to males that might lead to more robustness and has to be taken into account for the development of new anti-schistosomal drugs. Keywords Schistosoma mansoni . Tegument integrity . Human serum . Ultrastructural analysis

Introduction Schistosomiasis is considered the most important helminthic disease of humanity in terms of morbidity and mortality rates, affecting more than 200 million people mainly in the tropics and subtropics (Hotez et al. 2014). Estimates show that at least 229 million people required preventive treatment in 2018, out of which more than 97 million people were reported to have Section Editor: Xing-Quan ZHU * Martina Sombetzki [email protected] 1

Division of Tropical Medicine and Infectious Diseases, Center of Internal Medicine II, University Medical Center Rostock, Rostock, Germany

2

Medical Biology and Electron Microscopy Center, University Medical Center Rostock, Rostock, Germany

3

Department Life, Light and Matter, University of Rostock, Rostock, Germany

been treated (WHO 2018). Disease causing pathogens are parasitic flatworms of the genus Schistosoma spp. A chara