Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro

Enterohemorrhagic <i>Escherichia coli</i> (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing<i> E. coli</i> O157:H7 is the serotype most frequently associated with severe human disease. In this work...

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Main Authors: Andrea Cecilia Bruballa, Carolina Maiumi Shiromizu, Alan Mauro Bernal, Gonzalo Ezequiel Pineda, Florencia Sabbione, Analia Silvina Trevani, Leticia Verónica Bentancor, María Victoria Ramos, Romina Jimena Fernández-Brando, Manuel Javier Muñoz, Marina Sandra Palermo
Format: Article
Language:English
Published: MDPI AG 2020-01-01
Series:Toxins
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Online Access:https://www.mdpi.com/2072-6651/12/1/48
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author Andrea Cecilia Bruballa
Carolina Maiumi Shiromizu
Alan Mauro Bernal
Gonzalo Ezequiel Pineda
Florencia Sabbione
Analia Silvina Trevani
Leticia Verónica Bentancor
María Victoria Ramos
Romina Jimena Fernández-Brando
Manuel Javier Muñoz
Marina Sandra Palermo
author_facet Andrea Cecilia Bruballa
Carolina Maiumi Shiromizu
Alan Mauro Bernal
Gonzalo Ezequiel Pineda
Florencia Sabbione
Analia Silvina Trevani
Leticia Verónica Bentancor
María Victoria Ramos
Romina Jimena Fernández-Brando
Manuel Javier Muñoz
Marina Sandra Palermo
author_sort Andrea Cecilia Bruballa
collection DOAJ
description Enterohemorrhagic <i>Escherichia coli</i> (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing<i> E. coli</i> O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells participate in Stx2 production, cell damage, and inflammation during EHEC infection. With this aim, macrophage-differentiated THP-1 cells and the intestinal epithelial cell line HCT-8 were incubated with <i>E. coli</i> O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, <i>stx</i><sub>2</sub> transcription, and cytokine secretion were analyzed in both human cell lines. We demonstrated that macrophages are able to internalize and kill EHEC. Simultaneously, Stx2 produced by internalized bacteria played a major role in macrophage death. In contrast, HCT-8 cells were completely resistant to EHEC infection. Besides, macrophages and HCT-8 infected cells produce IL-1&#946; and IL-8 inflammatory cytokines, respectively. At the same time, bacterial <i>stx</i><sub>2</sub>-specific transcripts were detected only in macrophages after EHEC infection. The interplay between bacteria and host cells led to Stx production, triggering of inflammatory response and cell damage, all of which could contribute to a severe outcome after EHEC infections.
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spelling doaj.art-796379e3b5b342b0af3b1a76c6a065502022-12-22T02:17:52ZengMDPI AGToxins2072-66512020-01-011214810.3390/toxins12010048toxins12010048Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitroAndrea Cecilia Bruballa0Carolina Maiumi Shiromizu1Alan Mauro Bernal2Gonzalo Ezequiel Pineda3Florencia Sabbione4Analia Silvina Trevani5Leticia Verónica Bentancor6María Victoria Ramos7Romina Jimena Fernández-Brando8Manuel Javier Muñoz9Marina Sandra Palermo10Laboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Ingeniería Genética y Biología Celular y Molecular, Universidad Nacional de Quilmes, Buenos Aires 1876, ArgentinaLaboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaLaboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaInstituto de Fisiología, Biología Molecular y Neurociencias (IFIBYNE-UBA-CONICET), Departamento de Fisiología, Biología Molecular y Celular and Departamento de Biodiversidad y Biología Experimental, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Buenos Aires C1428EHA, ArgentinaLaboratorio de Patogénesis e Inmunología de Procesos Infecciosos, Instituto de Medicina Experimental (IMEX), Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires C1425AUM, ArgentinaEnterohemorrhagic <i>Escherichia coli</i> (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing<i> E. coli</i> O157:H7 is the serotype most frequently associated with severe human disease. In this work we analyzed the hypothesis that host cells participate in Stx2 production, cell damage, and inflammation during EHEC infection. With this aim, macrophage-differentiated THP-1 cells and the intestinal epithelial cell line HCT-8 were incubated with <i>E. coli</i> O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, <i>stx</i><sub>2</sub> transcription, and cytokine secretion were analyzed in both human cell lines. We demonstrated that macrophages are able to internalize and kill EHEC. Simultaneously, Stx2 produced by internalized bacteria played a major role in macrophage death. In contrast, HCT-8 cells were completely resistant to EHEC infection. Besides, macrophages and HCT-8 infected cells produce IL-1&#946; and IL-8 inflammatory cytokines, respectively. At the same time, bacterial <i>stx</i><sub>2</sub>-specific transcripts were detected only in macrophages after EHEC infection. The interplay between bacteria and host cells led to Stx production, triggering of inflammatory response and cell damage, all of which could contribute to a severe outcome after EHEC infections.https://www.mdpi.com/2072-6651/12/1/48ehecstx2stx2macrophagesintestinal epithelial cellsil-1βil-8mrna
spellingShingle Andrea Cecilia Bruballa
Carolina Maiumi Shiromizu
Alan Mauro Bernal
Gonzalo Ezequiel Pineda
Florencia Sabbione
Analia Silvina Trevani
Leticia Verónica Bentancor
María Victoria Ramos
Romina Jimena Fernández-Brando
Manuel Javier Muñoz
Marina Sandra Palermo
Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
Toxins
ehec
stx2
stx2
macrophages
intestinal epithelial cells
il-1β
il-8
mrna
title Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
title_full Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
title_fullStr Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
title_full_unstemmed Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
title_short Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of <i>Escherichia coli</i> O157:H7 during Host-Bacterial Interactions in vitro
title_sort role of shiga toxins in cytotoxicity and immunomodulatory effects of i escherichia coli i o157 h7 during host bacterial interactions in vitro
topic ehec
stx2
stx2
macrophages
intestinal epithelial cells
il-1β
il-8
mrna
url https://www.mdpi.com/2072-6651/12/1/48
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