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Correlation between intestinal BMP2, IFN?, and neural death in experimental infection with Trypanosoma cruzi.

ABSTRACT: 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, IFN?, TNF-?, and IL-10 quantification. The infection induced increased intestinal IFN? 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 IFN?. In the same analyzed period, BMP2 and IFN? 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.

SUBMITTER: do Carmo Neto JR

PROVIDER: S-EPMC7872263 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi.

do Carmo Neto José Rodrigues JR Vinicius da Silva Marcos M Braga Yarlla Loyane Lira YLL Florencio da Costa Arthur Wilson AW Fonseca Simone Gonçalves SG Nagib Patricia Resende Alô PRA Nunes Celes Mara Rúbia MR Oliveira Milton Adriano Pelli MAP Machado Juliana Reis JR

PloS one 20210209 2

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 ...[more]

PMID: 33561140

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Project description:Chagas' disease is a parasitosis caused by Trypanosoma cruzi, which affects approximately 8 million people worldwide. The balance between pro- and anti-inflammatory cytokines produced during immunological responses contributes to disease prognosis and progression. Parasite tissue persistence can induce chronic inflammatory stimuli, which can cause long-term tissue injury and fibrosis. Chronic Chagas' patients exhibit increased levels of interleukin (IL)-9, an important cytokine in the regulation of inflammatory and fibrogenic processes. Data on the role of IL-9 in other pathologies are sometimes contradictory, and few studies have explored this cytokine's influence in Chagas' disease pathology. Hence, the aim of this study was to evaluate the role of IL-9 in the progression of T. cruzi infection in vivo and in vitro. In vitro infection demonstrated that IL-9 reduced the number of infected cells and decreased the multiplication of intracellular amastigotes in both C2C12 myoblasts and bone marrow-derived macrophages. In myoblasts, the increased production of nitric oxide (NO) was essential for reduced parasite multiplication, whereas macrophage responses resulted in increased IL-6 and reduced TGF-β levels, indicating that parasite growth restriction mechanisms induced by IL-9 were cell-type specific. Experimental infection of BALB/c mice with T. cruzi trypomastigotes of the Y strain implicated a major role of IL-9 during the chronic phase, as increased Th9 and Tc9 cells were detected among splenocytes; higher levels of IL-9 in these cell populations and increased cardiac IL-9 levels were detected compared to those of uninfected mice. Moreover, rIL9 treatment decreased serum IL-12, IL-6, and IL-10 levels and cardiac TNF-α levels, possibly attempting to control the inflammatory response. IL-9 neutralization increased cardiac fibrosis, synthesis of collagens I and III, and mastocyte recruitment in BALB/c heart tissue during the chronic phase. In conclusion, our data showed that IL-9 reduced the invasion and multiplication of T. cruzi in vitro, in both myoblasts and macrophages, favoring disease control through cell-specific mechanisms. In vivo, IL-9 was elevated during experimental chronic infection in BALB/c mice, and this cytokine played a protective role in the immunopathological response during this phase by controlling cardiac fibrosis and proinflammatory cytokine production.

Dataset Information

Correlation between intestinal BMP2, IFN?, and neural death in experimental infection with Trypanosoma cruzi.

Publications

Correlation between intestinal BMP2, IFNγ, and neural death in experimental infection with Trypanosoma cruzi.

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