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Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response

View ORCID ProfileKevin K. Takaki, View ORCID ProfileFrancisco J. Roca, Gabriele Schramm, View ORCID ProfileRuud H. P. Wilbers, View ORCID ProfileWannaporn Ittiprasert, Paul J. Brindley, View ORCID ProfileGabriel Rinaldi, Matthew Berriman, View ORCID ProfileLalita Ramakrishnan, View ORCID ProfileAntonio J. Pagán
doi: https://doi.org/10.1101/2020.09.29.318105
Kevin K. Takaki
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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Francisco J. Roca
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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Gabriele Schramm
2Experimental Pneumology, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research (DZL), Borstel, Germany
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Ruud H. P. Wilbers
3Laboratory of Nematology, Plant Sciences Group, Wageningen University and Research, Droevendaalsesteeg, The Netherlands
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Wannaporn Ittiprasert
4Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States
5Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States
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Paul J. Brindley
4Department of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States
5Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington University, Washington, DC, United States
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Gabriel Rinaldi
6Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
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Matthew Berriman
6Wellcome Sanger Institute, Wellcome Genome Campus, Hinxton, United Kingdom
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Lalita Ramakrishnan
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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  • For correspondence: lr404@cam.ac.uk ap825@cam.ac.uk
Antonio J. Pagán
1Molecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular Biology, Cambridge, United Kingdom
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  • For correspondence: lr404@cam.ac.uk ap825@cam.ac.uk
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Abstract

Infections by schistosomes result in granulomatous lesions around parasite eggs entrapped within the host tissues. The host and parasite determinants of the Schistosoma mansoni egg-induced granulomatous response are areas of active investigation. Some studies in mice implicate Tumor Necrosis Factor (TNF) produced in response to the infection whereas others fail to find a role for it. In addition, in the mouse model, the S. mansoni secreted egg antigen omega-1 is found to induce granulomas but the underlying mechanism remains unknown. We have recently developed the zebrafish larva as a model to study macrophage recruitment and granuloma formation in response to Schistosoma mansoni eggs. Here we use this model to investigate the mechanisms by which TNF and omega-1 shape the early granulomatous response. We find that TNF, specifically signaling through TNF receptor 1, is not required for macrophage recruitment to the egg and granuloma initiation but does mediate granuloma enlargement. In contrast, omega-1 mediates initial macrophage recruitment, with this chemotactic activity being dependent on its RNase activity. Our findings further the understanding of the role of these host- and parasite-derived factors and show that they impact distinct facets of the granulomatous response to the schistosome egg.

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Posted September 29, 2020.
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Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response
Kevin K. Takaki, Francisco J. Roca, Gabriele Schramm, Ruud H. P. Wilbers, Wannaporn Ittiprasert, Paul J. Brindley, Gabriel Rinaldi, Matthew Berriman, Lalita Ramakrishnan, Antonio J. Pagán
bioRxiv 2020.09.29.318105; doi: https://doi.org/10.1101/2020.09.29.318105
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Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response
Kevin K. Takaki, Francisco J. Roca, Gabriele Schramm, Ruud H. P. Wilbers, Wannaporn Ittiprasert, Paul J. Brindley, Gabriel Rinaldi, Matthew Berriman, Lalita Ramakrishnan, Antonio J. Pagán
bioRxiv 2020.09.29.318105; doi: https://doi.org/10.1101/2020.09.29.318105

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