Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

Anisuzzaman; Sören Frahm; Ulrich Fabien Prodjinotho; Sonakshi Bhattacharjee; Admar Verschoor; Clarissa Prazeres da Costa

doi:10.3389/fimmu.2021.635622

Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

Anisuzzaman, Sören Frahm, Ulrich Fabien Prodjinotho, Sonakshi Bhattacharjee, Admar Verschoor, Clarissa Prazeres da Costa^*

^*Corresponding author for this work

Institute of Systemic Inflammation Research

Technical University of Munich

14 Citations (Scopus)

Abstract

Introduction: Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage of Schistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies. Materials and Methods: Using our recently developed novel serum- and cell-free in vitro culture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgM in vitro and assessed worm development in vivo by infecting complement and soluble (s)IgM-deficient animals. Results: In contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stage in vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice with S. mansoni as well as in vitro tests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factors in vivo in regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice. Conclusion: This study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.

Original language	English
Article number	635622
Journal	Frontiers in Immunology
Volume	12
Pages (from-to)	635622
ISSN	1664-3224
DOIs	https://doi.org/10.3389/fimmu.2021.635622
Publication status	Published - 23.04.2021

Funding

We would like to thank Sabine Paul, Ulla Henn, Stephanie Fetzer and Marija Ram for excellent technical help and maintenance of the schistosome life-cycle. Many thanks to Prof. Markus Gerhard (MIH, Technical University of Munich (TUM)) and the German Primate Center (DPZ, G?ttingen, Germany) for kindly providing the sera from S. mansoni -na?ve non-human primates (NHP, rhesus macaques) and TUM Center for Preclinical Research (CPR) for providing sera from horses, swine, sheep, hamsters, rabbits and rats. We would like to thank Laura Hunt for careful proof-reading of the manuscript. Financial support was provided by DFG 1469/15-1. SF was supported by the doctoral program in Translational Medicine of the TUM School of medicine. A was supported by a postdoctoral fellowship for foreign researchers by the Alexander von Humboldt Foundation (Georg Foster Program).

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research Areas and Centers

Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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10.3389/fimmu.2021.635622

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title = "Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni",

abstract = "Introduction: Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage of Schistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30\% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies. Materials and Methods: Using our recently developed novel serum- and cell-free in vitro culture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgM in vitro and assessed worm development in vivo by infecting complement and soluble (s)IgM-deficient animals. Results: In contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stage in vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice with S. mansoni as well as in vitro tests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factors in vivo in regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice. Conclusion: This study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.",

author = "Anisuzzaman and S{\"o}ren Frahm and Prodjinotho, \{Ulrich Fabien\} and Sonakshi Bhattacharjee and Admar Verschoor and \{Prazeres da Costa\}, Clarissa",

note = "Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Anisuzzaman, Frahm, Prodjinotho, Bhattacharjee, Verschoor and Prazeres da Costa.",

year = "2021",

month = apr,

day = "23",

doi = "10.3389/fimmu.2021.635622",

language = "English",

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T1 - Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

AU - Anisuzzaman,

AU - Frahm, Sören

AU - Prodjinotho, Ulrich Fabien

AU - Bhattacharjee, Sonakshi

AU - Verschoor, Admar

AU - Prazeres da Costa, Clarissa

PY - 2021/4/23

Y1 - 2021/4/23

N2 - Introduction: Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage of Schistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies. Materials and Methods: Using our recently developed novel serum- and cell-free in vitro culture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgM in vitro and assessed worm development in vivo by infecting complement and soluble (s)IgM-deficient animals. Results: In contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stage in vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice with S. mansoni as well as in vitro tests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factors in vivo in regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice. Conclusion: This study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.

AB - Introduction: Schistosomiasis is a neglected tropical disease (NTD) caused by blood-dwelling flatworms which develop from skin-penetrating cercariae, the freely swimming water-borne infective stage of Schistosoma mansoni, into adult worms. This natural course of infection can be mimicked in experimental mouse models of schistosomiasis. However, only a maximum of 20-30% of penetrated cercariae mature into fecund adults. The reasons for this are unknown but could potentially involve soluble factors of the innate immune system, such as complement factors and preexisting, natural antibodies. Materials and Methods: Using our recently developed novel serum- and cell-free in vitro culture system for newly transformed schistosomula (NTS), which supports long-term larval survival, we investigated the effects of mouse serum and its major soluble complement factors C1q, C3, C4 as well as preexisting, natural IgM in vitro and assessed worm development in vivo by infecting complement and soluble (s)IgM-deficient animals. Results: In contrast to sera from humans and a broad variety of mammalian species, serum from mice, surprisingly, killed parasites already at skin stage in vitro. Interestingly, the most efficient killing component(s) were heat-labile but did not include important members of the perhaps best known family of heat-labile serum factors, the complement system, nor consisted of complement-activating natural immunoglobulins. Infection of complement C1q and sIgM-deficient mice with S. mansoni as well as in vitro tests with sera from mice deficient in C3 and C4 revealed no major role for these soluble factors in vivo in regard to parasite maturation, fecundity and associated immunopathology. Rather, the reduction of parasite maturation from cercariae to adult worms was comparable to wild-type mice. Conclusion: This study reveals that not yet identified heat-labile serum factors are major selective determinants of the host-specificity of schistosomiasis, by directly controlling schistosomal development and survival.

UR - https://www.scopus.com/pages/publications/85105494869

U2 - 10.3389/fimmu.2021.635622

DO - 10.3389/fimmu.2021.635622

M3 - Journal articles

C2 - 33968028

AN - SCOPUS:85105494869

SN - 1664-3224

VL - 12

SP - 635622

JO - Frontiers in Immunology

JF - Frontiers in Immunology

M1 - 635622

ER -

Host-Specific Serum Factors Control the Development and Survival of Schistosoma mansoni

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