Stereotypic and specific elements of the human colonic response to Entamoeba histolytica and Shigella flexneri

Summary The clinical presentations of bacillary dysentery caused by shigella, and amoebic dysentery caused by the protozoan parasite Entamoeba histolytica, can be indistinguishable, with both organisms causing colonic mucosal damage and ulceration. However, the two organisms are quite distinct, and have very different pathogenic mechanisms. This raises the fundamental question of whether the similar clinical manifestations reflect a stereotypic response of the human gut to mucosal injury, or whether there are differences at the molecular level in the host response to individual gut pathogens. To characterize the human colonic response to each pathogen at the molecular level, we measured the differential transcription of nearly 40 000 human genes in sections of human colonic xenografts obtained 4 and 24 h following infection with Shigella flexneri or E. histolytica. Our results indicate that much of the human colonic response to these two pathogens is stereotypic, with increased expression of genes activated in cells undergoing stress and/or hypoxic responses, genes encoding cytokines, chemokines, and mediators that are involved in immune and inflammatory responses, and genes encoding proteins involved in responses to tissue injury and in tissue repair. The responses to amoeba and Shigella were not identical however, and we found unique elements in each response that may provide new insights into the distinct pathogenic mechanisms of E. histolytica and S. flexneri.