Martins Patrícia Rocha, Nascimento Rodolfo Duarte, Dos Santos Aline Tomaz, de Oliveira Enio Chaves, Martinelli Patricia Massara, d'Avila Reis Débora
Morphology Department, Federal University of Minas Gerais, Belo Horizonte, 31.270-901, Brazil.
Centre for Education and Research at Institute Mario Penna, Belo Horizonte, Brazil.
Parasitol Res. 2018 Apr;117(4):1147-1158. doi: 10.1007/s00436-018-5792-z. Epub 2018 Feb 22.
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.
恰加斯病是由克氏锥虫寄生虫引起的一种感染，全球数百万人受其影响，在拉丁美洲为地方病。巨结肠是消化慢性型最常见的并发症，是由肠神经系统损伤所致。神经元损伤似乎在急性期开始，并在慢性期持续存在，尽管这一过程涉及的机制仍存在争议。在可能参与这一病理过程的免疫系统细胞中，肥大细胞（MC）因其在免疫和神经系统双向通信中的众所周知的作用而备受关注。通过超微结构分析，我们发现与未感染对照组相比，感染患者中靠近神经纤维的脱颗粒MC数量增加。我们还对MC进行免疫染色，检测两种促炎分子组织蛋白酶和糜蛋白酶，其中前者在神经元死亡中也很重要。巨结肠患者中组织蛋白酶或糜蛋白酶免疫染色的MC数量增加，而在无巨结肠患者中还观察到组织蛋白酶染色增加。此外，我们在肠神经系统的神经元中检测到组织蛋白酶受体PAR2的表达，这与组织蛋白酶染色结果相关。总之，本文提供的数据表明MC参与了克氏锥虫诱导的巨结肠发展过程中发生的去神经支配过程。
