Original contributionGlial fibrillary acidic protein and S-100 colocalization in the enteroglial cells in dilated and nondilated portions of colon from chagasic patients☆
Introduction
Chagas' disease (American trypanosomiasis), which is caused by the protozoan Trypanosoma cruzi, is endemic in Central and South America. The parasite is most commonly transmitted to humans by hematophagous insects of the Reduviidae family [1]. The infection has a self-limited acute phase, detected only in a minority of infected persons. In the chronic form of Chagas' disease, cardiac and gastrointestinal involvement may occur, depending on multiple factors, including the host immune response [2], [3], [4].
The gastrointestinal form of Chagas' disease is characterized mainly by the involvement of the esophagus and colon. Previous studies demonstrated that colon dilatation and lengthening lead to megacolon development. Abnormalities of the enteric nervous system (ENS), namely, degeneration and neuronal number reduction, seem to be essential elements in the pathogenesis of the gastrointestinal disorders [3], [5], [6]. Actually, it is thought that neuronal loss occurs because of immune cytotoxic mechanisms [6], [7] and parasite-induced lesions [7], [8], [9]. Ultramicroscopic studies of colon from acutely infected patients have demonstrated that T cruzi penetrates a variety of cells such as macrophages, neurons, and enteric glia cells (EGCs).
EGCs play an important role in the maintenance of gastrointestinal tract tissue integrity. The exact mechanisms by which EGCs contribute to gut homeostasis are still poorly understood [10], [11], although recent data have demonstrated that, when stimulated with proinflammatory cytokines, EGCs represent the main source of neurotrophic factors in the gut [12]. S-100 is a Ca2+-binding protein commonly used to identify EGCs, whereas glial fibrillary acidic protein (GFAP) is expressed by only a subpopulation of EGCs, principally in the presence of inflammatory factors [13]. It has been suggested that enhanced expression of GFAP by EGCs could represent a structural barrier against immune cytotoxic mechanisms to enteric neurons.
The present study was designed based on our hypothesis that in the colon of T cruzi–infected patients, the EGCs might have an active response because of inflammatory cytokines secreted by immune cells. If this is true, the functional state of EGCs might determine the level of neuronal loss and the development of megacolon. To test our hypothesis, we performed double-labeling immunohistochemistry for S-100 and GFAP to characterize the EGCs present in dilated and nondilated portions of colon from patients with chronic chagasic megacolon. We further looked for correlations between the EGC phenotype and the number of enteric neurons to determine the relationship between these ENS components in chagasic patients.
Section snippets
Patients and tissue collection
Colon tissue samples were collected from noninfected individuals (n = 5) and chagasic patients with megacolon (n = 10). Patient characteristics are shown in Table 1. The main reasons for tissue resection were colon complications caused by Chagas' disease in chagasic patients and adenocarcinoma or diverticular disease in noninfected individuals. All surgical specimens were collected from the same topographic regions of the colon (rectum and sigmoid) during low anterior resection or a Duhamel
Analysis of the inflammatory process
H&E sections of dilated and nondilated portions of the colon from patients with megacolon and from noninfected individuals were studied to determine the intensity of the inflammatory process. The dilated portions from chagasic patients demonstrated an intense inflammatory infiltrate with predominantly mononuclear cells. However, the nondilated portions from chagasic patients and from noninfected individuals did not show any significant inflammatory process. Histologic sections of colon samples
Discussion
The etiology of the pathogenesis and physiopathology of chagasic megacolon is the least understood clinical form of Chagas' disease. The relationship among colon dilatation, the extent of the numerical reduction in neurons, and the alteration of EGCs is an important feature that needs to be understood. Many studies on chagasic megacolon have evaluated only neuronal destruction [3], [5], [15]. In addition, EGCs in chagasic megacolon have not been investigated. This is the first report evaluating
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Effects of resveratrol on the differentiation fate of neural progenitor cells of mouse embryos infected with Trypanosoma cruzi
2019, Microbial PathogenesisCitation Excerpt :In situation of brain injury and parasite infection, inflammatory stimuli occur, such as cytokine production . The increase in GFAP+ cells is related to the capability of the parasite to release PDNF [29], ensuring the immune response of the CNS [33,36]. Moreover, RSV contributed to stimulating gliogenesis in acute T. cruzi infection during brain development.
Histological and immunohistochemical studies of changes in myenteric plexuses and in interstitial cells of Cajal associated with equine colic
2012, Research in Veterinary ScienceEnteroglial cells act as antigen-presenting cells in chagasic megacolon
2011, Human PathologyCitation Excerpt :Differences were considered statistically significant at P < .05. Our previous results demonstrated that chagasic patients have clear neuronal reduction and destruction of EGCs in both the submucosal and the myenteric plexuses [5,6]. In this study, our data demonstrated that the HLA-DR class II molecule is not expressed in the EGCs of noninfected individuals (Fig. 1).
Neurodegeneration and neuroregeneration in chagas disease
2011, Advances in ParasitologyCitation Excerpt :That neuronal regeneration is taking place in CD and can be important for the clinical status of infected patients is indicated by the comparative physiological and pathological studies which revealed substantial differences in the extent of organ innervations between asymptomatic and chronic CD patients. While neuronal deficiency in the symptomatic group correlated with poor functional characteristics, asymptomatic patients with better neuronal counts showed normal electrocardiogram and X-rays of the heart, oesophagus and colon, and were not much different to seronegative controls (Correia et al., 2007; da Silveira et al., 2005, 2009; Junqueira and Soares, 2002; Koberle, 1970; Marin-Neto, 1998; Nascimento et al., 2010; Villar et al., 2004). The direct demonstration of autonomic recovery after the acute phase of T. cruzi infection was further provided by experimental CD models.
Characterization of enteroglial cells and denervation process in chagasic patients with and without megaesophagus
2010, Human PathologyCitation Excerpt :Previous studies demonstrated that, in the whole gastrointestinal tract, other components of the enteric nervous system respond to inflammatory process. These components are the enteroglial cells [9,10]. Enteroglial cells perform an important role in the maintenance of enteric nervous system in the gastrointestinal tract.
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This work was supported by funds from CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico) Ministério da Ciência e Tecnologia, Brazil, and the National Health and Medical Research Council of Australia (grant 400020).