An imbalance between substance P and vasoactive intestinal polypeptide might contribute to the immunopathology of megaesophagus after Trypanosoma cruzi infection

Nascimento, Rodolfo Duarte; Martins, Patrícia; Lisboa, André de Souza; Adad, Sheila Jorge; Silveira, Alexandre Barcelos Morais da; Reis, Débora d’Ávila

doi:10.1016/j.humpath.2012.05.020

Cited by 16 publications

(18 citation statements)

References 29 publications

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“…The decrease of substance P and VIP could be the result of denervation of the myenteric plexus observed in those mice, and could be related to the disturbances in intestinal motility observed in the chronic phase of Chagas disease (72). Nascimento and co-workers studied the expression of substance P and VIP in megaesophagus of chagasic individuals, which are known to activate or inhibit local immune cells, respectively (73). Morphometric analyses revealed increased substance P- and decreased VIP-reactive areas in esophageal sections from patients with megaesophagus.…”

Section: Interactions Between the Neuroendocrine And Immune Systems Imentioning

confidence: 99%

Immunoregulatory networks in human Chagas disease

Dutra

Menezes

Magalhães

et al. 2014

Parasite Immunology

136

133

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Summary Chagas disease, caused by the infection with Trypanosoma cruzi, is endemic in all Latin America. Due to the increase in population migration, Chagas disease has spread worldwide and is now considered a health issue not only in endemic countries. While most chronically infected individuals remain asymptomatic, approximately 30% of the patients develop a potentially deadly cardiomyopathy. The exact mechanisms that underlie the establishment and maintenance of the cardiac pathology are not clear. However, there is consistent evidence that immunoregulatory cytokines are critical for orchestrating the immune response and, thus, influence disease development or control. While the asymptomatic (indeterminate) form represents a state of balance between the host and the parasite, the establishment of the cardiac form represents the loss of this balance. Analysis of data obtained from several studies have led to the hypothesis that the indeterminate form is associated with an anti-inflammatory cytokine profile, represented by high expression of IL-10, while cardiac form is associated with a high production of IFN-gamma and TNF-alpha in relation to IL-10, leading to an inflammatory profile. Here, we discuss the immunoregulatory events that might influence disease outcome, as well as the mechanisms that influence the establishment of these complex immunoregulatory networks.

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Section: Interactions Between the Neuroendocrine And Immune Systems Imentioning

confidence: 99%

Immunoregulatory networks in human Chagas disease

Dutra

Menezes

Magalhães

et al. 2014

Parasite Immunology

136

133

View full text Add to dashboard Cite

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“…Individuals with chagasic megaesophagus usually present dysphasia, peristaltic dysfunction and achalasia, and partial or absent lower esophageal sphincter relaxation [4] witch develop in consequence of the denervation [5,6]. Structural damage of the Enteric Nervous System (ENS), denervation above 90% in the myenteric plexus [7], ganglionitis and periganglionitis have been widely described in the digestive form of Chagas disease [8,9].…”

Section: Introductionmentioning

confidence: 99%

Decrease of Nitrergic Innervation in the Esophagus of Patients with Chagas Disease: Correlation with Loss of Interstitial Cells of Cajal

Nascimento¹,

Martins²,

Duarte³

et al. 2017

Int J Pathol Clin Res

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The pathogenesis of megaesophagus in chronic Chagas disease, which is caused by infection with the parasite Trypanosoma cruzi is compelling. Individuals with megaesophagus often present achalasia and disturbances of peristalsis and neuronal loss. Esophageal samples were obtained from 6 T. cruzi infected individuals with megaesophagus, 6 T. cruzi infected individuals without megaesophagus, and 6 noninfected individuals who underwent necropsy procedures. Using one antibody specific for neuronal Nitric Oxide Synthase (nNOS) and another specific for Protein Gene Product 9.5 (PGP-9.5), which is a pan-neuronal marker, we demonstrated the relative area of nitrergic innervation. Additionally, we analysed the area occupied by Interstitial Cells of Cajal (ICCs) with antibody specific anti-CD117. The analyses presented here show that the relative area of nitrergic innervation is reduced in T. cruzi infected individuals with megaesophagus. Furthermore, we demonstrated reduced CD117-immunostained areas in the esophagus of T. cruzi infected individuals. Statistical analyses revealed a positive correlation between the relative area of nitrergic innervation and the density of ICCs in the same infected individuals. Considering data from the literature, we raised the hypothesis that the loss of nitrergic nerve fibers and ICCs could be view as an interdependent phenomenon occurring in the esophagus of T. cruzi infected individuals and that it could contribute to peristalsis disturbances, to achalasia and to megaesophagus development.

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“…Some authors have suggested that the survival imbalance between excitatory and inhibitory motor myenteric neurons is strongly associated with the pathogenesis of chagasic megacolon . In this sense, we observed a higher nitrergic myenteric neuronal survival compared to that for cholinergic myenteric neurons in the T. cruzi infected mice treated with PBS, which was associated with delayed gastrointestinal transit, however, no megacolon was observed in these mice.…”

Section: Discussionmentioning

confidence: 99%