Epithelial cell-initiated inflammation plays a crucial role in early tissue damage in amebic infection of human intestine

Background & Aims: Entamoeba histolytica infection of the intestine can ind uce severe gut inflammation. The aims of this study were to assess the role of the host inflammatory response in the tissue damage observed with amebi asis and the role of the intestinal epithelial cell in initiating that resp onse. Methods: E. histolytica infection was established in human intestinal xenografts in severe combined immunodeficient (SCID-HU-INT) mice. Human in testinal epithelial cell inflammatory responses to amebic infection were in hibited by the intraluminal administration of an antisense oligonucleotide to the human p65 subunit of nuclear factor KB, and the role of neutrophils in tissue damage observed with amebiasis was studied by depleting neutrophi ls from SCID-HU-INT mice. Results: Administration of the antisense oligonuc leotide blocked the production of human interleukin 1 beta and interleukin 8 by intestinal epithelial cells and inhibited neutrophil influx into the E . histolytica-infected intestinal xenografts. Inhibition of the gut inflamm atory response by the antisense oligonucleotide or the depletion of neutrop hils from SCID-HU-INT mice blocked the increase in intestinal permeability observed with amebic infection. Conclusions: Intestinal epithelial cells in itiate an inflammatory response with resulting neutrophil-mediated tissue d amage in response to E. histolytica infection; this inflammatory cascade ca n be blocked by inhibiting the transcription of genes regulated by nuclear factor KB.