Tissue Destruction Caused by Entamoeba histolytica Parasite : Cell Death, Inflammation, Invasion, and the Gut Microbiome

Abstract

Purpose of review: Entamoeba histolytica is a protozoan parasite that causes amebiasis, which remains a significant cause of morbidity and mortality worldwide. E. histolytica causes tissue destruction which leads to clinical disease. This review outlines some of the recent advances that have furthered our understanding of the processes that lead to the tissue damage caused by E. histolytica.

Recent findings: Recent studies have identified new mechanisms involved in E. histolytica-induced tissue damage. These include (i) new form of contact-dependent killing called trogocytosis; (ii) parasite-produced cytokine, macrophage migration inhibitory factor, that contributes to inflammation; (iii) exploitation of host immune response to promote invasion; and (iv) the contribution of the gut microbiome to clinical disease.

Summary: Targeting these mechanisms that result in tissue injury should be a focus of future research for the development of improved preventive and therapeutic strategies for amebiasis.

Keywords: Amebiasis; E. histolytica macrophage migration inhibitory factor; Invasion; Microbiome; Trogocytosis.

Fig. 1

Patient with amebic colitis. a Intestinal ulcers due to E. histolyica.bE. histolyica within the lamina propria (arrows) surrounded by inflammatory infiltrate of neutrophils. c Invasion of intestinal mucosa by amebic trophozoites. Immunohistochemical staining of trophozoites (brown) using specific anti–Entamoeba histolytica macrophage migration inhibitory factor antibodies. Panels (a, b) are reproduced from [4] and (C) from [••] with permission

Fig. 2

Pathogenesis of intestinal amebiasis. 1. Secreted E. histolytica macrophage migration inhibitory factor (EhMIF) promotes mucosal inflammation. 2. E. histolytica–induced inflammation results in increased production in matrix metalloproteinases (MMPs) which break down extracellular matrix (ECM) in the gut to promote cell migration. 3. Infiltrating inflammatory cells generate oxygen free radicals (ROS) which are capable of killing parasites. Oxygen free radicals are also responsible for collateral tissue damage during the inflammatory period. 4. E. histolytica invades the intestinal mucosa by evading and exploiting the host immune system. 5. Contact-dependent cell killing by E. histolytica. 6. Elevated levels of P. copri increases the risk of colitis