Pathogenesis of intestinal amebiasis: from molecules to disease

Abstract

In spite of a wealth of knowledge on the biochemistry and cellular and molecular biology of Entamoeba histolytica, little has been done to apply these advances to our understanding of the lesions observed in patients with intestinal amebiasis. In this review, the pathological and histological findings in acute amebic colitis are related to the molecular mechanisms of E. histolytica pathogenicity described to date. Infection of the human colon by E. histolytica produces focal ulceration of the intestinal mucosa, resulting in dysentery (diarrhea with blood and mucus). Although a complete picture has not yet been achieved, the basic mechanisms involved in the production of focal lytic lesions include complex multifactorial processes in which lectins facilitate adhesion, proteases degrade extracellular matrix components, porins help nourish the parasite and may also kill incoming polymorphonuclear leukocytes and macrophages, and motility is used by the parasite to invade deeper layers of the colon. In addition, E. histolytica has developed mechanisms to modulate the immune response during acute infection. Nevertheless, much still needs to be unraveled to understand how this microscopic parasite has earned its well-deserved histolytic name.

FIG. 1

Intestinal specimen from a patient with acute amebic colitis. Several nodular lesions show characteristic rounded, slightly elevated areas of the mucosa with irregular necrotic centers surrounded by edematous hyperemic tissue. The necrotic centers are filled with a yellowish mucoid material, except in two ulcers, where the center is hemorrhagic. The intervening mucosal folds have a mostly normal appearance, although one segment is congested and edematous.

FIG. 2

Experimental intestinal amebiasis in the guinea pig. An invading E. histolytica trophozoite proceeds through the interglandular epithelium. A large pseudopod is extended by the parasite during penetration to the lamina propria. A semithin section stained with toluidine blue is shown.

FIG. 3

Scanning electron micrographs of experimental intestinal amebiasis in the guinea pig. (A) Trophozoites of E. histolytica adhere preferentially to the elevated interglandular epithelium. (B) A small interglandular region of microinvasion is observed in the early invasive lesion with superficial ulceration. (C) In a more advanced stage of invasion, numerous trophozoites are seen penetrating a colonic ulcer.