Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi.
Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi.
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DOI：
10.1371/journal.pone.0246692
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发表时间：
2021
期刊：
影响因子：
3.7
通讯作者：
Machado JR
中科院分区：
文献类型：
--
作者：
do Carmo Neto JR;Vinicius da Silva M;Braga YLL;Florencio da Costa AW;Fonseca SG;Nagib PRA;Nunes Celes MR;Oliveira MAP;Machado JR
巨结肠是恰加斯病的主要晚期并发症之一，影响约10%的有症状患者。然而，需要研究来了解这种情况进展的机制。在克氏锥虫（T.克氏）感染期间，炎症谱开始形成，与神经死亡有关，这种破坏已知是巨结肠进展所必需的。与肠道神经元维持相关的蛋白质之一是2型骨形态发生蛋白（BMP2）。肠道BMP2稳态直接参与器官功能的维持。因此，本研究的目的是在感染T. cruzi Y株的C57Bl/6小鼠急性期和慢性期，将肠道BMP2的产生与免疫病理变化联系起来。小鼠感染了1000种血锥马鞭毛虫。安乐死后，收集结肠，将其分成两段，一半用于组织学分析，另一半用于BMP2、IFNγ、TNF-α和IL-10定量。感染引起急性期肠道IFNγ和BMP2生成增加，炎症浸润增加。相反，在这一阶段，观察到肌肠丛神经元数量减少。在整个感染过程中胶原沉积逐渐增加，表现为慢性期。此外，急性期BMP2的升高与肠道IFNγ呈正相关。在同一时间段内，BMP2和IFNγ与肌肠丛神经元数量呈负相关。作为首次报道的克氏t细胞感染后BMP2改变，我们认为这种不平衡不仅与神经元损伤有关，而且可能代表了在急性期维持肠道促炎谱的新途径。
Megacolon is one of the main late complications of Chagas disease, affecting approximately 10% of symptomatic patients. However, studies are needed to understand the mechanisms involved in the progression of this condition. During infection by Trypanosoma cruzi (T. cruzi), an inflammatory profile sets in that is involved in neural death, and this destruction is known to be essential for megacolon progression. One of the proteins related to the maintenance of intestinal neurons is the type 2 bone morphogenetic protein (BMP2). Intestinal BMP2 homeostasis is directly involved in the maintenance of organ function. Thus, the aim of this study was to correlate the production of intestinal BMP2 with immunopathological changes in C57Bl/6 mice infected with the T. cruzi Y strain in the acute and chronic phases. The mice were infected with 1000 blood trypomastigote forms. After euthanasia, the colon was collected, divided into two fragments, and a half was used for histological analysis and the other half for BMP2, IFNγ, TNF-α, and IL-10 quantification. The infection induced increased intestinal IFNγ and BMP2 production during the acute phase as well as an increase in the inflammatory infiltrate. In contrast, a decreased number of neurons in the myenteric plexus were observed during this phase. Collagen deposition increased gradually throughout the infection, as demonstrated in the chronic phase. Additionally, a BMP2 increase during the acute phase was positively correlated with intestinal IFNγ. In the same analyzed period, BMP2 and IFNγ showed negative correlations with the number of neurons in the myenteric plexus. As the first report of BMP2 alteration after infection by T. cruzi, we suggest that this imbalance is not only related to neuronal damage but may also represent a new route for maintaining the intestinal proinflammatory profile during the acute phase.
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影响因子：
2
作者：
de Souza AP;Sieberg R;Li H;Cahill HR;Zhao D;Araújo-Jorge TC;Tanowitz HB;Jelicks LA
通讯作者：
Jelicks LA
影响因子：
2.4
作者：
da Silveira, ABM;Arantes, RME;Reis, DD
通讯作者：
Reis, DD
影响因子：
7.3
作者：
Bleuming, S. A.;Kodach, L. L.;van den Brink, G. R.
通讯作者：
van den Brink, G. R.
DOI：
10.1590/0001-3765201920180389
发表时间：
2019-01-01
期刊：
Anais da Academia Brasileira de Ciências
影响因子：
--
作者：
SOUZA, NOEMI D. DE;BELIN, BRUNA S.;MOREIRA, NEIDE M.
通讯作者：
MOREIRA, NEIDE M.
影响因子：
4.6
作者：
da Silva, Marcos Vinicius;de Almeida, Vera Lucia;Machado, Juliana Reis
通讯作者：
Machado, Juliana Reis