Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay

Xiaofeng Du; Donald P. McManus; Conor E. Fogarty; Malcolm K. Jones; Hong You

doi:10.3389/fimmu.2022.868077

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Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay

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Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay

Xiaofeng Du, Donald P. McManus, Conor E. Fogarty, Malcolm K. Jones and Hong You

Frontiers in Immunology, Vol.13, pp.1-15

2022

DOI: https://doi.org/10.3389/fimmu.2022.868077

PMCID: PMC9257043

PMID: 35812433

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Abstract

fibroblast growth factor receptor A

host-parasite interplay

immunolocalization

Schistosoma mansoni

stem cell marker

Stem cells play significant roles in driving the complex life cycle of Schistosoma mansoni. Fibroblast growth factor (FGF) receptor A (SmFGFRA) is essential for maintaining the integrity of schistosome stem cells. Using immunolocalization, we demonstrated that SmFGFRA was distributed abundantly in germinal/stem cells of different S. mansoni life stages including eggs, miracidia, cercariae, schistosomula and adult worms. Indeed, SmFGFRA was also localized amply in embryonic cells and in the perinuclear region of immature eggs; von Lichtenberg’s layer and the neural mass of mature eggs; the ciliated surface and neural mass of miracidia; the tegument cytosol of cercariae, schistosomula and adult worms; and was present in abundance in the testis and vitellaria of adult worms of S. mansoni. The distribution pattern of SmFGFRA illustrates the importance of this molecule in maintaining stem cells, development of the nervous and reproductive system of schistosomes, and in the host-parasite interplay. We showed SmFGFRA can bind human FGFs, activating the mitogen activated protein kinase (MAPK) pathway of adult worms in vitro. Inhibition of FGF signaling by the specific tyrosine kinase inhibitor BIBF 1120 significantly reduced egg hatching ability and affected the behavior of miracidia hatched from the treated eggs, emphasizing the importance of FGF signaling in driving the life cycle of S. mansoni. Our findings provide increased understanding of the complex schistosome life cycle and host-parasite interactions, indicating components of the FGF signaling pathway may represent promising targets for developing new interventions against schistosomiasis.

Details

Title: Schistosoma mansoni Fibroblast Growth Factor Receptor A Orchestrates Multiple Functions in Schistosome Biology and in the Host-Parasite Interplay
Authors: Xiaofeng Du (Author) - Infection and Inflammation Program, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
Donald P. McManus (Author) - QIMR Berghofer Medical Research Institute
Conor E. Fogarty (Author) - University of the Sunshine Coast
Malcolm K. Jones (Author) - The University of Queensland
Hong You (Corresponding Author) - QIMR Berghofer Medical Research Institute
Publication details: Frontiers in Immunology, Vol.13, pp.1-15
Publisher: Frontiers Research Foundation
Date published: 2022
DOI: 10.3389/fimmu.2022.868077
ISSN: 1664-3224
PMID: 35812433; PMC9257043
Copyright note: Copyright © 2022 Du, McManus, Fogarty, Jones and You. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Data Availability: The original contributions presented in the study are included in the article/Supplementary Material. Further inquiries can be directed to the corresponding author.
Grants: Australian Government Research Training Program (RTP) Scholarship, RTP, Department of Education (Australia, Canberra)
Tropical diseases: Translating discoveries into better health, 1132975, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Conquering schistosomiasis in China: the last mile, 1098244, National Health and Medical Research Council (Australia, Canberra) - NHMRC
A worm-free world: defeating parasitic helminths via global integrated control, 1194462, National Health and Medical Research Council (Australia, Canberra) - NHMRC
Grant note: HY holds a QIMR Berghofer Medical Research Institute Seed Funding Grant (SF-210005).
Organisation Unit: GeneCology Research Centre - Legacy; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99656594502621
Output Type: Journal article

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