New insights into amebiasis using a human 3D-intestinal model

Entamoeba histolytica, the agent of amebiasis, colonizes the human colon and can invade the lining of the colon to disseminate in the deep layers of the intestine. Amebiasis mainly affects poor people in developing countries, where the barriers between human feces and food or water are inadequate. Humans are the only reservoir of E. histolytica and are the sole target organism of the development of the disease, which limits our knowledge of the crosstalk between the colon and the parasite, especially during the acute phase of amebiasis. In the present work, we constructed a three-Dimensional (3D)-intestinal model capable of reproducing important features of the human intestine. Using this model and leading-edge technologies, including tissue and cell imaging, transcriptomics, and proteomics, as well as ELISA-based immune response inspection, the early stages of amebic infection have been studied. The data obtained highlight the importance of several virulence markers already shown in patients or experimental models, but also underscore the involvement of other factors that appear to be key regulators of gene expression or important in the secretome of the infected tissue. In addition, we characterized the cellular stress responses against amebiasis and novel regulatory mechanisms utilized by this parasite to modulate the immune response and survive within the human intestine.