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ANALYSIS OF INTESTINAL INVASION PROCESS BY E. HISTOLYTICA USING ORGANOID-DERIVED 2D MONOLAYERS (ID 328)
Abstract
Introduction
Entamoeba histolytica is the causative agent of amoebiasis. E. histolytica can live in the human intestine for months or years without causing symptoms in the host. For reasons that are still unclear, the amoebae can suddenly destroy the intestinal mucosa and become invasive. This can lead to amoebic colitis or extraintestinal amoebic liver abscesses. To analyze the invasion process, only very artificial animal models exist so far.
Methods
We are trying to better understand the invasion process using human intestinal organoid-derived 2D monolayers and clones as well as transfectants of E. histolytica that differ in pathogenicity.
Results
Preliminary results indicate that pathogenic and non-pathogenic amoebae can invade a human organoid-derived 2D monolayer at the same rate. Inhibition of cysteine peptidases, which are postulated to be an important factor in the invasion process, significantly reduce monolayer destruction only in pathogenic amoebae. In contrast, inhibition of metallopeptidases leads to significant reduction of monolayer destruction only by the non-pathogenic amoebae.
After 4-hour co-incubation of non-pathogenic amoebae with the 2D monolayer, 260 human genes were identified as significantly differentially expressed. In contrast, co-incubation with pathogenic amoebae significantly changed the expression of only 48 genes. The genes most affected by regulation are those encoding proteins of the immune system.
Conclusions
Through this result, it can be postulated that the non-pathogenic amoebae stimulate the immune system more and are therefore better eliminated than the pathogenic amoebae.
This work is supported by the Deutsche Forschungsgemeinschaft (BR 1744).