Dogs infected with the blood trypomastigote form of Trypanosoma cruzi display an increase expression of cytokines and chemokines plus an intense cardiac parasitism during acute infection

Abstract

The recent increase in immigration of people from areas endemic for Chagas disease (Trypanosoma cruzi) to the United States and Europe has raised concerns about the transmission via blood transfusion and organ transplants in these countries. Infection by these pathways occurs through blood trypomastigotes (BT), and these forms of T. cruzi are completely distinct of metacyclic trypomastigotes (MT), released by triatomine vector, in relation to parasite-host interaction. Thus, research comparing infection with these different infective forms is important for explaining the potential impacts on the disease course. Here, we investigated tissue parasitism and relative mRNA expression of cytokines, chemokines, and chemokine receptors in the heart during acute infection by MT or BT forms in dogs. BT-infected dogs presented a higher cardiac parasitism, increased relative mRNA expression of pro-inflammatory and immunomodulatory cytokines and of the chemokines CCL3/MIP-1α, CCL5/RANTES, and the chemokine receptor CCR5 during the acute phase of infection, as compared to MT-infected dogs. These results suggest that infection with BT forms may lead to an increased immune response, as revealed by the cytokines ratio, but this kind of immune response was not able to control the cardiac parasitism. Infection with the MT form presented an increase in the relative mRNA expression of IL-12p40 as compared to that of IL-10 or TGF-β1. Correlation analysis showed increased relative mRNA expression of IFN-γ as well as IL-10, which may be an immunomodulatory response, as well as an increase in the correlation of CCL5/RANTES and its CCR5 receptor. Our findings revealed a difference between inoculum sources of T. cruzi, as vectorial or transfusional routes of T. cruzi infection may trigger distinct parasite-host interactions during the acute phase, which may influence immunopathological aspects of Chagas disease.

CCL3/Macrophage Inflammatory Protein-1α Is Dually Involved in Parasite Persistence and Induction of a TNF- and IFNγ-Enriched Inflammatory Milieu in Trypanosoma cruzi-Induced Chronic Cardiomyopathy

“…Corroborating these data, our results disclosed an increase in CCL3 mRNA expression in the hearts and spleens of acute and chronically Colombian-infected C57BL/6 mice. Similarly, increased CCL3 mRNA expression was detected in the heart tissue of C57BL/6 mice and hamsters infected with the Y type II strain (34,35), rats infected with the CL-Brener type VI strain (36) and dogs infected with the Berenice-78 strain type II strain (37). In addition, we showed high levels of CCL3 protein in the cardiac tissue of acute and chronically infected C57BL6 mice, as previously shown in C3H/He mice (15).…”

Modulatory Effect of Trypanosoma cruzi Infective Stages in Different Dendritic Cell Populations in vitro

“…Previous reports with mTp obtained from culture or the vector and bTp from mouse infection showed differences in the immune response associated with the stage of the parasite involved. In a dog experimental model, animals presented enhanced cardiac parasitism and inflammatory response when infected with bTp, suggesting that the inoculum source affects the immunopathological aspects of Chagas disease (de Souza et al, 2014). In addition, it was also demonstrated in a mouse model of infection that bTps were more virulent than culture mTps, via both oral and peritoneal inoculation (Dias et al, 2013), concluding and remarking on the importance of the stage used, its origin, and the model of the infection in order to study the immune response.…”

“…In the mammal host, two stages are present, the intracellular multiplicative amastigotes and bloodstream trypomastigotes (bTp), involved in the parasite dissemination to tissues. While vectorial and oral transmission involves mTp entry via injured skin or mucous membranes, parasite dissemination in the mammalian host occurs by bTp, also responsible for congenital and sanguineous transmission even in non-endemic regions (de Souza et al, 2014;OMS, 2019).…”

Genetically Determined MBL Deficiency Is Associated with Protection against Chronic Cardiomyopathy in Chagas Disease

“…This effect could be dependent on multimeric MBL forms, known to regulate the release of different cytokines from monocytes and other immune cells in response to infection [ 31 , 59 ]. Although IL-9 was not yet implicated in CD, PDGF was associated with proliferative lesions and fibrosis in CCC [ 60 ] and RANTES is among the highest expressed genes in dogs with intense cardiac parasitism and in end-stage CCC patients [ 61 , 62 ]. All these findings allow speculation for the use of inhibitors of the lectin pathway, as a preventive therapy to reduce tissue injury in inflammatory cardiac disorders and other chronic inflammatory diseases where activation of the lectin pathway takes place [ 63 ].…”