Research Article: The Interplay between Entamoeba and Enteropathogenic Bacteria Modulates Epithelial Cell Damage

Date Published: July 23, 2008

Publisher: Public Library of Science

Author(s): José Manuel Galván-Moroyoqui, M. del Carmen Domínguez-Robles, Elizabeth Franco, Isaura Meza, Photini Sinnis

Abstract: BackgroundMixed intestinal infections with Entamoeba histolytica, Entamoeba dispar and bacteria with exacerbated manifestations of disease are common in regions where amoebiasis is endemic. However, amoeba–bacteria interactions remain largely unexamined.MethodologyTrophozoites of E. histolytica and E. dispar were co-cultured with enteropathogenic bacteria strains Escherichia coli (EPEC), Shigella dysenteriae and a commensal Escherichia coli. Amoebae that phagocytosed bacteria were tested for a cytopathic effect on epithelial cell monolayers. Cysteine proteinase activity, adhesion and cell surface concentration of Gal/GalNAc lectin were analyzed in amoebae showing increased virulence. Structural and functional changes and induction of IL-8 expression were determined in epithelial cells before and after exposure to bacteria. Chemotaxis of amoebae and neutrophils to human IL-8 and conditioned culture media from epithelial cells exposed to bacteria was quantified.Principal FindingsE. histolytica digested phagocytosed bacteria, although S. dysenteriae retained 70% viability after ingestion. Phagocytosis of pathogenic bacteria augmented the cytopathic effect of E. histolytica and increased expression of Gal/GalNAc lectin on the amoebic surface and increased cysteine proteinase activity. E. dispar remained avirulent. Adhesion of amoebae and damage to cells exposed to bacteria were increased. Additional increases were observed if amoebae had phagocytosed bacteria. Co-culture of epithelial cells with enteropathogenic bacteria disrupted monolayer permeability and induced expression of IL-8. Media from these co-cultures and human recombinant IL-8 were similarly chemotactic for neutrophils and E. histolytica.ConclusionsEpithelial monolayers exposed to enteropathogenic bacteria become more susceptible to E. histolytica damage. At the same time, phagocytosis of pathogenic bacteria by amoebae further increased epithelial cell damage.SignificanceThe in vitro system presented here provides evidence that the Entamoeba/enteropathogenic bacteria interplay modulates epithelial cell responses to the pathogens. In mixed intestinal infections, where such interactions are possible, they could influence the outcome of disease. The results offer insights to continue research on this phenomenon.

Partial Text: Once trophozoites of Entamoeba histolytica reach the host intestine, they can damage the mucosa epithelial layer and spread through the submucosa and the lamina propia and other tissues. Neutrophils and other cells infiltrate the tissue in the vicinity of amoebic lesions increasing the inflammatory response and tissue damage [1],[2]. In contrast, Entamoeba dispar, an amoeba that colonizes the human intestine together with E. histolytica and that is morphologically indistinguishable and genetically very similar to the latter, is not invasive and does not produce the clinical manifestations of an E. histolytica intestinal infection [3],[4],[5].

When trophozoites of Entamoeba histolytica invade the host intestinal mucosa, they can cause inflammatory colitis. However, trophozoites can remain in the colon without causing tissue damage. Phagocytosis of bacteria, regularly present in the colonic flora, has been considered a possible stimulus to induce amoebic invasive behavior. In regions were E. histolytica and E. dispar are endemic, it is common that intestinal infections caused by enteropathogenic bacteria occur simultaneously with the presence of amoebae [21],[22],[23],[24],[25],[26]. In these conditions, it is also common to find exacerbated manifestations of the infection. It is then feasible that the interplay between pathogens modulates amoebic virulence and the response of the intestinal epithelial cells.



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