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Open AccessArticle

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

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Laboratorio 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, Argentina
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Laboratorio de Inmunidad Innata, Instituto de Medicina Experimental (IMEX)-CONICET, Academia Nacional de Medicina, Buenos Aires C1425AUM, Argentina
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Laboratorio de Ingeniería Genética y Biología Celular y Molecular, Universidad Nacional de Quilmes, Buenos Aires 1876, Argentina
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Instituto 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, Argentina
*
Author to whom correspondence should be addressed.
Toxins 2020, 12(1), 48; https://doi.org/10.3390/toxins12010048
Received: 8 November 2019 / Revised: 10 January 2020 / Accepted: 11 January 2020 / Published: 14 January 2020
Enterohemorrhagic Escherichia coli (EHEC) strains are food-borne pathogens that can cause different clinical conditions. Shiga toxin 2a and/or 2c (Stx2)-producing E. coli 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 E. coli O157:H7. A time course analysis of cellular and bacterial survival, Stx2 production, stx2 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-1β and IL-8 inflammatory cytokines, respectively. At the same time, bacterial stx2-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.
Keywords: EHEC; Stx2; stx2; macrophages; intestinal epithelial cells; IL-1β; IL-8; mRNA EHEC; Stx2; stx2; macrophages; intestinal epithelial cells; IL-1β; IL-8; mRNA
MDPI and ACS Style

Bruballa, A.C.; Shiromizu, C.M.; Bernal, A.M.; Pineda, G.E.; Sabbione, F.; Trevani, A.S.; Bentancor, L.V.; Ramos, M.V.; Fernández-Brando, R.J.; Muñoz, M.J.; Palermo, M.S. Role of Shiga Toxins in Cytotoxicity and Immunomodulatory Effects of Escherichia coli O157:H7 during Host-Bacterial Interactions in vitro. Toxins 2020, 12, 48.

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