Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes

The hemolytic uremic syndrome associated with diarrhea, a consequence of Shiga toxin (Stx)-producing Escherichia coli infection, is a common cause of pediatric acute renal failure in Argentina. Stx type 2a (Stx2a) causes direct damage to renal cells and induces local inflammatory responses that invo...

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Autores principales:	David Antonio Rosso, Micaela Rosato, Fernando Daniel Gómez, Romina Soledad Álvarez, Carolina Maiumi Shiromizu, Irene Angélica Keitelman, Cristina Ibarra, María Marta Amaral, Carolina Cristina Jancic
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	γδ T cells hemolytic uremic syndrome Shiga toxin type 2 inflammation Th1-like profile Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/22f5710744ee4bba9c70de79b4795ae6
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spelling	oai:doaj.org-article:22f5710744ee4bba9c70de79b4795ae62021-12-01T02:02:31ZHuman Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes2235-298810.3389/fcimb.2021.765941https://doaj.org/article/22f5710744ee4bba9c70de79b4795ae62021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcimb.2021.765941/fullhttps://doaj.org/toc/2235-2988The hemolytic uremic syndrome associated with diarrhea, a consequence of Shiga toxin (Stx)-producing Escherichia coli infection, is a common cause of pediatric acute renal failure in Argentina. Stx type 2a (Stx2a) causes direct damage to renal cells and induces local inflammatory responses that involve secretion of inflammatory mediators and the recruitment of innate immune cells. γδ T cells constitute a subset of T lymphocytes, which act as early sensors of cellular stress and infection. They can exert cytotoxicity against infected and transformed cells, and produce cytokines and chemokines. In this study, we investigated the activation of human peripheral γδ T cells in response to the incubation with Stx2a-stimulated human glomerular endothelial cells (HGEC) or their conditioned medium, by analyzing in γδ T lymphocytes, the expression of CD69, CD107a, and perforin, and the production of TNF-α and IFN-γ. In addition, we evaluated by confocal microscopy the contact between γδ T cells and HGEC. This analysis showed an augmentation in cellular interactions in the presence of Stx2a-stimulated HGEC compared to untreated HGEC. Furthermore, we observed an increase in cytokine production and CD107a expression, together with a decrease in intracellular perforin when γδ T cells were incubated with Stx2a-treated HGEC or their conditioned medium. Interestingly, the blocking of TNF-α by Etanercept reversed the changes in the parameters measured in γδ T cells incubated with Stx2a-treated HGEC supernatants. Altogether, our results suggest that soluble factors released by Stx2a-stimulated HGEC modulate the activation of γδ T cells, being TNF-α a key player during this process.David Antonio RossoMicaela RosatoFernando Daniel GómezRomina Soledad ÁlvarezCarolina Maiumi ShiromizuIrene Angélica KeitelmanCristina IbarraMaría Marta AmaralCarolina Cristina JancicCarolina Cristina JancicFrontiers Media S.A.articleγδ T cellshemolytic uremic syndromeShiga toxin type 2inflammationTh1-like profileMicrobiologyQR1-502ENFrontiers in Cellular and Infection Microbiology, Vol 11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	γδ T cells hemolytic uremic syndrome Shiga toxin type 2 inflammation Th1-like profile Microbiology QR1-502
spellingShingle	γδ T cells hemolytic uremic syndrome Shiga toxin type 2 inflammation Th1-like profile Microbiology QR1-502 David Antonio Rosso Micaela Rosato Fernando Daniel Gómez Romina Soledad Álvarez Carolina Maiumi Shiromizu Irene Angélica Keitelman Cristina Ibarra María Marta Amaral Carolina Cristina Jancic Carolina Cristina Jancic Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
description	The hemolytic uremic syndrome associated with diarrhea, a consequence of Shiga toxin (Stx)-producing Escherichia coli infection, is a common cause of pediatric acute renal failure in Argentina. Stx type 2a (Stx2a) causes direct damage to renal cells and induces local inflammatory responses that involve secretion of inflammatory mediators and the recruitment of innate immune cells. γδ T cells constitute a subset of T lymphocytes, which act as early sensors of cellular stress and infection. They can exert cytotoxicity against infected and transformed cells, and produce cytokines and chemokines. In this study, we investigated the activation of human peripheral γδ T cells in response to the incubation with Stx2a-stimulated human glomerular endothelial cells (HGEC) or their conditioned medium, by analyzing in γδ T lymphocytes, the expression of CD69, CD107a, and perforin, and the production of TNF-α and IFN-γ. In addition, we evaluated by confocal microscopy the contact between γδ T cells and HGEC. This analysis showed an augmentation in cellular interactions in the presence of Stx2a-stimulated HGEC compared to untreated HGEC. Furthermore, we observed an increase in cytokine production and CD107a expression, together with a decrease in intracellular perforin when γδ T cells were incubated with Stx2a-treated HGEC or their conditioned medium. Interestingly, the blocking of TNF-α by Etanercept reversed the changes in the parameters measured in γδ T cells incubated with Stx2a-treated HGEC supernatants. Altogether, our results suggest that soluble factors released by Stx2a-stimulated HGEC modulate the activation of γδ T cells, being TNF-α a key player during this process.
format	article
author	David Antonio Rosso Micaela Rosato Fernando Daniel Gómez Romina Soledad Álvarez Carolina Maiumi Shiromizu Irene Angélica Keitelman Cristina Ibarra María Marta Amaral Carolina Cristina Jancic Carolina Cristina Jancic
author_facet	David Antonio Rosso Micaela Rosato Fernando Daniel Gómez Romina Soledad Álvarez Carolina Maiumi Shiromizu Irene Angélica Keitelman Cristina Ibarra María Marta Amaral Carolina Cristina Jancic Carolina Cristina Jancic
author_sort	David Antonio Rosso
title	Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
title_short	Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
title_full	Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
title_fullStr	Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
title_full_unstemmed	Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes
title_sort	human glomerular endothelial cells treated with shiga toxin type 2 activate γδ t lymphocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/22f5710744ee4bba9c70de79b4795ae6
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Human Glomerular Endothelial Cells Treated With Shiga Toxin Type 2 Activate γδ T Lymphocytes

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