The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis

Infection with intravascular platyhelminths of the genus Schistosoma can result in the debilitating disease schistosomiasis. Schistosomes (blood flukes) can survive in the host for many years. We hypothesize that proteins on their host-interactive surface modify the worm’s external environment to he...

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Autores principales:	Catherine S. Nation, Akram A. Da’Dara, Patrick J. Skelly
Formato:	article
Lenguaje:	EN
Publicado:	Taylor & Francis Group 2020
Materias:	schistosoma nad purinergic signaling tregs immunomodulation Infectious and parasitic diseases RC109-216
Acceso en línea:	https://doaj.org/article/4783348f8ee441e7ada5d28a2f1dea9c
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spelling	oai:doaj.org-article:4783348f8ee441e7ada5d28a2f1dea9c2021-11-17T14:21:58ZThe essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis2150-55942150-560810.1080/21505594.2020.1770481https://doaj.org/article/4783348f8ee441e7ada5d28a2f1dea9c2020-12-01T00:00:00Zhttp://dx.doi.org/10.1080/21505594.2020.1770481https://doaj.org/toc/2150-5594https://doaj.org/toc/2150-5608Infection with intravascular platyhelminths of the genus Schistosoma can result in the debilitating disease schistosomiasis. Schistosomes (blood flukes) can survive in the host for many years. We hypothesize that proteins on their host-interactive surface modify the worm’s external environment to help insure worm survival. Previously, we have shown that a surface ectoenzyme of Schistosoma mansoni, SmNPP5 – a nucleotide pyrophosphatase/phosphodiesterase – can cleave ADP and block platelet aggregation in vitro. In this work, we show that both adult schistosomes and recombinant SmNPP5 can cleave the exogenous purinergic signaling molecule nicotinamide adenine dinucleotide (NAD). In doing so, worms and rSmNPP5 can prevent NAD-induced apoptosis of T cells in vitro. Since regulatory T cells (Tregs) are especially prone to such NAD-induced cell death (NICD), we hypothesize that schistosome cleavage of NAD promotes Treg survival which creates a more immunologically hospitable environment for the worms in vivo. In addition to SmNPP5, schistosomes express another host-interactive NAD-degrading enzyme, SmNACE. We successfully suppressed the expression of SmNPP5 and SmNACE (singly or together) using RNAi. Only SmNPP5-suppressed worms, and not SmNACE-suppressed worms, were significantly impaired in their ability to cleave exogenous NAD compared to controls. Therefore, we contend that ectoenzyme SmNPP5 on the surface of the worm is primarily responsible for extracellular NAD cleavage and that this helps modulate the host immune environment by preventing Treg cell death.Catherine S. NationAkram A. Da’DaraPatrick J. SkellyTaylor & Francis Grouparticleschistosomanadpurinergic signalingtregsimmunomodulationInfectious and parasitic diseasesRC109-216ENVirulence, Vol 11, Iss 1, Pp 568-579 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	schistosoma nad purinergic signaling tregs immunomodulation Infectious and parasitic diseases RC109-216
spellingShingle	schistosoma nad purinergic signaling tregs immunomodulation Infectious and parasitic diseases RC109-216 Catherine S. Nation Akram A. Da’Dara Patrick J. Skelly The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
description	Infection with intravascular platyhelminths of the genus Schistosoma can result in the debilitating disease schistosomiasis. Schistosomes (blood flukes) can survive in the host for many years. We hypothesize that proteins on their host-interactive surface modify the worm’s external environment to help insure worm survival. Previously, we have shown that a surface ectoenzyme of Schistosoma mansoni, SmNPP5 – a nucleotide pyrophosphatase/phosphodiesterase – can cleave ADP and block platelet aggregation in vitro. In this work, we show that both adult schistosomes and recombinant SmNPP5 can cleave the exogenous purinergic signaling molecule nicotinamide adenine dinucleotide (NAD). In doing so, worms and rSmNPP5 can prevent NAD-induced apoptosis of T cells in vitro. Since regulatory T cells (Tregs) are especially prone to such NAD-induced cell death (NICD), we hypothesize that schistosome cleavage of NAD promotes Treg survival which creates a more immunologically hospitable environment for the worms in vivo. In addition to SmNPP5, schistosomes express another host-interactive NAD-degrading enzyme, SmNACE. We successfully suppressed the expression of SmNPP5 and SmNACE (singly or together) using RNAi. Only SmNPP5-suppressed worms, and not SmNACE-suppressed worms, were significantly impaired in their ability to cleave exogenous NAD compared to controls. Therefore, we contend that ectoenzyme SmNPP5 on the surface of the worm is primarily responsible for extracellular NAD cleavage and that this helps modulate the host immune environment by preventing Treg cell death.
format	article
author	Catherine S. Nation Akram A. Da’Dara Patrick J. Skelly
author_facet	Catherine S. Nation Akram A. Da’Dara Patrick J. Skelly
author_sort	Catherine S. Nation
title	The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
title_short	The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
title_full	The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
title_fullStr	The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
title_full_unstemmed	The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis
title_sort	essential schistosome tegumental ectoenzyme smnpp5 can block nad-induced t cell apoptosis
publisher	Taylor & Francis Group
publishDate	2020
url	https://doaj.org/article/4783348f8ee441e7ada5d28a2f1dea9c
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The essential schistosome tegumental ectoenzyme SmNPP5 can block NAD-induced T cell apoptosis

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