RESUMO
Chagas disease is an infection caused by the parasite Trypanosoma cruzi that affects millions of people worldwide and is endemic in Latin America. Megacolon is the most frequent complication of the digestive chronic form and happens due to lesions of the enteric nervous system. The neuronal lesions seem to initiate in the acute phase and persist during the chronic phase, albeit the mechanisms involved in this process are still debated. Among the cells of the immune system possibly involved in this pathological process is the mast cell (MC) due to its well-known role in the bi-directional communication between the immune and nervous systems. Using ultrastructural analysis, we found an increased number of degranulated MCs in close proximity to nerve fibers in infected patients when compared with uninfected controls. We also immunostained MCs for the two pro-inflammatory molecules tryptase and chymase, the first being also important in neuronal death. The number of MCs immunostained for tryptase or chymase was increased in patients with megacolon, whereas increased tryptase staining was additionally observed in patients without megacolon. Moreover, we detected the expression of the tryptase receptor PAR2 in neurons of the enteric nervous system, which correlated to the tryptase staining results. Altogether, the data presented herein point to the participation of MCs on the denervation process that occurs in the development of T. cruzi-induced megacolon.
Assuntos
Doença de Chagas/imunologia , Colo/patologia , Sistema Nervoso Entérico/imunologia , Mastócitos/imunologia , Megacolo/patologia , Neuroimunomodulação/fisiologia , Trypanosoma cruzi/imunologia , Idoso , Animais , Doença de Chagas/parasitologia , Quimases/imunologia , Besouros , Colo/parasitologia , Sistema Nervoso Entérico/parasitologia , Feminino , Humanos , Masculino , Megacolo/parasitologia , Pessoa de Meia-Idade , Neurônios/metabolismo , Receptor PAR-2 , Receptores Acoplados a Proteínas G/metabolismo , Triptases/imunologiaRESUMO
Chagas disease is one of the most serious parasitic diseases of Latin America, with a social and economic impact far outweighing the combined effects of other parasitic diseases such as malaria, leishmaniasis, and schistosomiasis. In the chronic phase of this disease, the destruction of enteric nervous system components leads to megacolon development. Besides neurons, the enteric nervous system is constituted by enteric glial cells, representing an extensive but relatively poorly described population within the gastrointestinal tract. Several lines of evidence suggest that enteric glial cells represent an equivalent of central nervous system astrocytes. Previous data suggest that enteric glia and neurons are active in the enteric nervous system during intestinal inflammatory and immune responses. To evaluate whether these cells act as antigen-presenting cells, we investigated the expression of molecules responsible for activation of T cells, such as HLA-DR complex class II and costimulatory molecules (CD80 and CD86), by neurons and enteric glial cells. Our results indicate that only enteric glial cells of chagasic patients with megacolon express HLA-DR complex class II and costimulatory molecules, and hence they present the attributes necessary to act as antigen-presenting cells.
Assuntos
Células Apresentadoras de Antígenos/imunologia , Doença de Chagas/imunologia , Megacolo Tóxico/imunologia , Neuroglia/imunologia , Adulto , Idoso , Antígeno B7-1/imunologia , Antígeno B7-2/imunologia , Doença de Chagas/complicações , Sistema Nervoso Entérico/imunologia , Feminino , Antígenos HLA-DR/imunologia , Humanos , Imuno-Histoquímica , Ativação Linfocitária/imunologia , Masculino , Megacolo Tóxico/microbiologia , Pessoa de Meia-IdadeRESUMO
The purpose of this work was to study the area of the varicosities of nerve fibers of myenteric neurons immunoreactive to vasoactive intestinal peptide (VIP-IR) and of the cell bodies of VIP-IR submucosal neurons of the jejunum of diabetic rats supplemented with 2% L-glutamine. Twenty male rats were divided into the following groups: normoglycemic (N), normoglycemic supplemented with L-glutamine (NG), diabetic (D) and diabetic supplemented with L-glutamine (DG). Whole-mounts of the muscle tunica and the submucosal layer were subjected to the immunohistochemical technique for neurotransmitter VIP identification. Morphometric analyses were carried out in 500 VIP-IR cell bodies of submucosal neurons and 2000 VIP-IR varicosities from each group. L-Glutamine supplementation to the normoglycemic animals caused an increase in the areas of the cell bodies (8.49%) and varicosities (21.3%) relative to the controls (P < 0.05). On the other hand, there was a decrease in the areas of the cell bodies (4.55%) and varicosities (28.9%) of group DG compared to those of group D (P < 0.05). It is concluded that L-glutamine supplementation was positive both to normoglycemic and diabetic animals.
Assuntos
Suplementos Nutricionais , Sistema Nervoso Entérico/patologia , Glutamina/administração & dosagem , Jejuno/inervação , Neurônios/patologia , Substâncias Protetoras/administração & dosagem , Peptídeo Intestinal Vasoativo/metabolismo , Aminoácidos Essenciais/administração & dosagem , Animais , Antioxidantes/administração & dosagem , Peso Corporal , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dieta , Sistema Nervoso Entérico/imunologia , Sistema Nervoso Entérico/metabolismo , Técnica Indireta de Fluorescência para Anticorpo , Hemoglobinas Glicadas , Jejuno/metabolismo , Jejuno/patologia , Masculino , Plexo Mientérico/imunologia , Plexo Mientérico/metabolismo , Plexo Mientérico/patologia , Neurônios/imunologia , Neurônios/metabolismo , Ratos , Ratos Wistar , Plexo Submucoso/imunologia , Plexo Submucoso/metabolismo , Plexo Submucoso/patologiaRESUMO
Most reports of autoimmune response during infection with the parasite Trypanosoma cruzi have dealt with the cardiomyopathic form of Chagas' disease, but little is known about the mechanisms of tissue damage involved in the gastrointestinal form, which was studied here. Chronically infected patients with a severe gastrointestinal form of Chagas' disease present increased antibody production and proliferative responses to peripheral myelin components, such as myelin basic protein (MBP), which is homologous to the P1 protein fraction of peripheral myelin. T lymphocytes preferentially recognize a region on the MBP molecule (1-30), which suggests that the MBP is a potential target on the peripheral nerve for autoimmune reactions in patients with gastrointestinal lesions resulting from Chagas' disease.
Assuntos
Doença de Chagas/imunologia , Sistema Nervoso Entérico/imunologia , Gastroenteropatias/imunologia , Bainha de Mielina/imunologia , Adulto , Animais , Autoanticorpos/imunologia , Autoantígenos/imunologia , Autoimunidade/imunologia , Encéfalo/imunologia , Encéfalo/patologia , Encéfalo/fisiopatologia , Doença de Chagas/fisiopatologia , Sistema Nervoso Entérico/patologia , Sistema Nervoso Entérico/fisiopatologia , Feminino , Gastroenteropatias/microbiologia , Gastroenteropatias/fisiopatologia , Trato Gastrointestinal/imunologia , Trato Gastrointestinal/inervação , Trato Gastrointestinal/fisiopatologia , Humanos , Ativação Linfocitária/imunologia , Masculino , Pessoa de Meia-Idade , Proteína Básica da Mielina/imunologia , Proteínas da Mielina/imunologia , Bainha de Mielina/patologia , Neurônios/imunologia , Neurônios/patologia , Nervos Periféricos/imunologia , Nervos Periféricos/patologia , Nervos Periféricos/fisiopatologia , Polirradiculoneuropatia/imunologia , Polirradiculoneuropatia/microbiologia , Polirradiculoneuropatia/fisiopatologia , Linfócitos T/imunologia , Trypanosoma cruzi/fisiologiaRESUMO
IgA was obtained from HIV-infected haemophilic patients and the intracellular signals triggered by its reaction with isolated rat intestinal strips were studied. HIV+ IgA stained intestinal microvilli with a granular immunofluorescence pattern and bound to the muscarinic acetylcholine receptor (mAChR), displacing the specific muscarinic cholinergic antagonist QNB in a non-competitive manner. It triggered the signals that are the consequence of mAChR stimulation in the intestine. Thus, it decreased cAMP synthesis and increased guanosine 3':5'-cyclic monophosphate (cGMP) formation and phosphoinositide (PI) turnover of the intestine. In addition, it stimulated prostaglandin E2(PGE2) synthesis by intestinal strips. Through its effect on PGE2 synthesis, HIV+ IgA could have a dual action. On the one hand, it could enhance immunosuppression at a local level, favouring pathogen growth and subsequent intestinal dysfunction. On the other hand, PGE2 could directly increase intestinal motility and electrolyte/fluid loss. Both effects could be involved in intestinal damage in AIDS.