Experimental amebiasis: a selected review of some in vivo models.
ABSTRACT The use of in vivo animal models in amebiasis has contributed significantly to the knowledge of this common human parasitic disease. Although there is no animal model that mimics the whole cycle of the human disease, the use of different susceptible and resistant laboratory animals and the availability for many years of techniques for the axenic culture of trophozoites of Entamoeba histolytica have allowed a better understanding of the parasite and the host-parasite relationship. The recent introduction of frontier methodologies in biology has increased our comprehension of this parasite. New information on the cellular and molecular biology and genetics of this organism has been extensively reported, and much of this has clearly required the more frequent use of animal models to verify specific facts. Based on experimental animals characterized previously, the introduction of new animal models with genetic or surgical modifications, especially in mice, has allowed a more adequate analysis of the mechanisms of pathogenesis. Multiple factors have been considered in the promotion of the invasiveness and virulence of E. histolytica. Additionally, the immunological and physiological responses of the host, depending on the environmental conditions, lead to the establishment or the rejection of the parasite. The role of inflammatory reaction to amebic infection constitutes one of the controversies that has been studied by several authors. In susceptible animals (hamsters and gerbils), inflammatory cell damage seems to be related to target cell lysis, while in resistant animals (mice), inflammatory cells appear to protect the host by lysing the parasite. Presently, the involvement of various substances in the development of lesions including lectins, proteases, amebapores, promoters of apoptosis, cytokines, nitric oxide, etc., is being examined using different in vivo models.
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ABSTRACT: Amoebiasis (a human intestinal infection affecting 50 million people every year) is caused by the protozoan parasite Entamoeba histolytica. To study the molecular mechanisms underlying human colon invasion by E. histolytica, we have set up an ex vivo human colon model to study the early steps in amoebiasis. Using scanning electron microscopy and histological analyses, we have established that E. histolytica caused the removal of the protective mucus coat during the first two hours of incubation, detached the enterocytes, and then penetrated into the lamina propria by following the crypts of Lieberkühn. Significant cell lysis (determined by the release of lactodehydrogenase) and inflammation (marked by the secretion of pro-inflammatory molecules such as interleukin 1 beta, interferon gamma, interleukin 6, interleukin 8 and tumour necrosis factor) were detected after four hours of incubation. Entamoeba dispar (a closely related non-pathogenic amoeba that also colonizes the human colon) was unable to invade colonic mucosa, lyse cells or induce an inflammatory response. We also examined the behaviour of trophozoites in which genes coding for known virulent factors (such as amoebapores, the Gal/GalNAc lectin and the cysteine protease 5 (CP-A5), which have major roles in cell death, adhesion (to target cells or mucus) and mucus degradation, respectively) were silenced, together with the corresponding tissue responses. Our data revealed that the signalling via the heavy chain Hgl2 or via the light chain Lgl1 of the Gal/GalNAc lectin is not essential to penetrate the human colonic mucosa. In addition, our study demonstrates that E. histolytica silenced for CP-A5 does not penetrate the colonic lamina propria and does not induce the host's pro-inflammatory cytokine secretion.PLoS Neglected Tropical Diseases 01/2009; 3(11):e551. · 4.69 Impact Factor
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ABSTRACT: Although Entamoeba dispar displays a similar morphology to Entamoeba histolytica, cellular and molecular studies have revealed significant differences between these two amoebae, including the former being characterized as non-pathogenic and the later as pathogenic. However, recent in vivo and in vitro experiments have shown that E. dispar strains of different origin are capable of causing liver damage and destroying cell culture lines in the presence of common intestinal bacteria. These results suggested that E. dispar may present pathogenic behavior according to the specific E. dispar strain, culture and environmental conditions. To investigate this possibility, we carried out in vivo and in vitro studies using a xenic strain E. dispar (ICB-ADO) isolated from a symptomatic non-dysenteric Brazilian patient. This strain was able to induce liver necrosis in a hamster model that was more severe than that produced by E. histolytica. The ICB-ADO isolate also caused significantly more destruction of cultured MDCK cells and increased loss of transepithelial resistance than did the E. histolytica. Xenic E. dispar exhibited high proteolytic activity, which was partially inhibited by the addition of cysteine-protease inhibitors. Based on our biochemical and molecular characterization of E. dispar (ICB-ADO) xenic culture and its ability to produce liver abscesses, we conclude that this specific strain can indeed produce tissue damage, distinct from the frequently used non- pathogenic E. dispar SAW 760 strain.Annals of hepatology: official journal of the Mexican Association of Hepatology 01/2012; 11(1):107-17. · 1.81 Impact Factor