Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response
Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response
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.
Wilbers Ruud H. P.、Berriman Matthew、Roca Francisco J.、Rinaldi Gabriel、Brindley Paul J.、Takaki Kevin K.、Ittiprasert Wannaporn、Ramakrishnan Lalita、Pag¨￠n Antonio J.、Schramm Gabriele
Laboratory of Nematology, Plant Sciences Group, Wageningen University and ResearchWellcome Sanger Institute, Wellcome Genome CampusMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular BiologyWellcome Sanger Institute, Wellcome Genome CampusDepartment of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University||Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington UniversityMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular BiologyDepartment of Microbiology, Immunology and Tropical Medicine, School of Medicine and Health Sciences, George Washington University||Research Center for Neglected Diseases of Poverty, School of Medicine and Health Sciences, George Washington UniversityMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular BiologyMolecular Immunity Unit, Department of Medicine, University of Cambridge, MRC Laboratory of Molecular BiologyExperimental Pneumology, Research Center Borstel, Airway Research Center North, Member of the German Center for Lung Research (DZL)
基础医学生物科学研究方法、生物科学研究技术微生物学
Wilbers Ruud H. P.,Berriman Matthew,Roca Francisco J.,Rinaldi Gabriel,Brindley Paul J.,Takaki Kevin K.,Ittiprasert Wannaporn,Ramakrishnan Lalita,Pag¨￠n Antonio J.,Schramm Gabriele.Tumor Necrosis Factor and Schistosoma mansoni egg antigen Omega-1 shape distinct aspects of the early egg-induced granulomatous response[EB/OL].(2025-03-28)[2025-05-26].https://www.biorxiv.org/content/10.1101/2020.09.29.318105.点此复制
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