Human Polymorphisms in Placentally Expressed Genes and Their Association With Susceptibility to Congenital<i>Trypanosoma cruzi</i>Infection

Juiz, Natalia Anahí; Cayo, Nelly Melina; Burgos, Marianela; Salvo, Miriam; Nasser, Julio R.; Búa, Jacqueline; Longhi, Silvia Andrea; Schijman, Alejandro G.

doi:10.1093/infdis/jiv561

Cited by 17 publications

(12 citation statements)

References 45 publications

(48 reference statements)

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“…8 Recently, it was published that the placental environment upregulates the innate immune response against infection by two stocks of T. cruzi in mice. 48 Here, we present data on some aspects of the innate immune system on the infection of placental chorionic villi explants by two stocks and two inocula of T. cruzi.…”

Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase and oxidative‐nitrosative stress play a key role in placental infection by Trypanosoma cruzi

Triquell

Díaz-Luján

Romanini

et al. 2018

American J Rep Immunol

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The higher number of parasites caused deleterious consequences to the placental barrier, and the inhibitors (l-NAME and NAC) prevented the damage caused by trypomastigotes in placental villi but not that of the infection. Moreover, trophoblast eNOS played a key role in placental infection with the highest inoculum of Lucky, demonstrating the importance of the enzyme and nitrosative-oxidative stress in Chagas congenital transmission.

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Section: Discussionmentioning

confidence: 99%

Nitric oxide synthase and oxidative‐nitrosative stress play a key role in placental infection by Trypanosoma cruzi

Triquell

Díaz-Luján

Romanini

et al. 2018

American J Rep Immunol

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“…Even though distinct strains may display subtle differences in their ability to invade trophoblasts or chorionic villi explants in vitro (Castillo et al, 2013), genetic profiling experiments have conclusively shown that i) the same set of strains circulate in the bloodstream of transmitting and non-transmitting mothers, and ii) nearly identical T. cruzi genetic signatures are recovered from infected infants born to Chagasic mothers coursing concurrent, multi-strain infections (Figure 1) (Burgos et al, 2007; del Puerto et al, 2010; Virreira et al, 2006a). Overall, the actual consensus is that maternal parasite load and human polymorphisms constitute the main risk factors for T. cruzi congenital transmission (Bua et al, 2012; Fabbro et al, 2014; Juiz et al, 2016; Kaplinski et al, 2015; Rendell et al, 2015). …”

Section: Trypanosoma Cruzi An 'All-wheel Drive' Parasitementioning

confidence: 99%

Chagas Disease Diagnostic Applications

Balouz

Agüero

Buscaglia

2017

Advances in Parasitology

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Chagas disease, caused by the protozoan Trypanosoma cruzi, is a life-long and debilitating illness of major significance throughout Latin America, and an emergent threat to global public health. Being a neglected disease, the vast majority of Chagasic patients have limited access to proper diagnosis and treatment, and there is only a marginal investment into R&D for drug and vaccine development. In this context, identification of novel biomarkers able to transcend the current limits of diagnostic methods surfaces as a main priority in Chagas disease applied research. The expectation is that these novel biomarkers will provide reliable, reproducible and accurate results irrespective of the genetic background, infecting parasite strain, stage of disease, and clinical-associated features of Chagasic populations. In addition, they should be able to address other still unmet diagnostic needs, including early detection of congenital T. cruzi transmission, rapid assessment of treatment efficiency or failure, indication/prediction of disease progression and direct parasite typification in clinical samples. The lack of access of poor and neglected populations to essential diagnostics also stress the necessity of developing new methods operational in Point-of-Care (PoC) settings. In summary, emergent diagnostic tests integrating these novel and tailored tools should provide a significant impact on the effectiveness of current intervention schemes and on the clinical management of Chagasic patients. In this chapter, we discuss the present knowledge and possible future steps in Chagas disease diagnostic applications, as well as the opportunity provided by recent advances in high-throughput methods for biomarker discovery.

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“…Chagas disease (American trypanosomiasis) is caused by the protozoa parasite Trypanosoma cruzi (T. cruzi), which is transmitted to humans by blood-sucking triatomine bugs and by non-vectorial mechanisms, such as contaminated blood transfusion, organ transplantation, and congenital infection [1,2]. Chagas disease is a significant public health burden and the leading cause of death and morbidity in Latin American and Caribbean regions [3].…”

Section: Introductionmentioning

confidence: 99%

Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas’ human cardiomyocytes

Mijares

Espinosa²,

Adams

et al. 2020

PLoS Negl Trop Dis

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Chagas cardiomyopathy is the most severe manifestation of human Chagas disease and represents the major cause of morbidity and mortality in Latin America. We previously demonstrated diastolic Ca 2+ alterations in cardiomyocytes isolated from Chagas' patients to different degrees of cardiac dysfunction. In addition, we have found a significant elevation of diastolic [Na + ] d in Chagas' cardiomyocytes (FCII>FCI) that was greater than control. Exposure of cardiomyocytes to agents that enhance inositol 1,4,5 trisphosphate (IP 3) generation or concentration like endothelin (ET-1) or bradykinin (BK), or membrane-permeant myoinositol 1,4,5-trisphosphate hexakis(butyryloxy-methyl) esters (IP 3 BM) caused an elevation in diastolic [Ca 2+ ] ([Ca 2+ ] d) that was always greater in cardiomyocytes from Chagas' than non-Chagas' subjects, and the magnitude of the [Ca 2+ ] d elevation in Chagas' cardiomyocytes was related to the degree of cardiac dysfunction. Incubation with xestospongin-C (Xest-C), a membrane-permeable selective blocker of the IP 3 receptors (IP 3 Rs), significantly reduced [Ca 2+ ] d in Chagas' cardiomyocytes but did not have a significant effect on non-Chagas' cells. The effects of ET-1, BK, and IP 3 BM on [Ca 2+ ] d were not modified by the removal of extracellular [Ca 2+ ] e. Furthermore, cardiomyocytes from Chagas' patients had a significant decrease in the sarcoplasmic reticulum (SR) Ca 2+ content compared to control (Control>F-CI>FCII), a higher intracellular IP 3 concentration ([IP 3 ] i) and markedly depressed contractile properties compared to control cardiomyocytes. These results provide additional and convincing support about the implications of IP 3 in the pathogenesis of Chagas cardiomyopathy in patients at different stages of chronic infection. Additionally, these findings open the door for novel therapeutic strategies oriented to improve cardiac function and quality of life of individuals suffering from chronic Chagas cardiomyopathy (CC).

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Human Polymorphisms in Placentally Expressed Genes and Their Association With Susceptibility to CongenitalTrypanosoma cruziInfection

Cited by 17 publications

References 45 publications

Nitric oxide synthase and oxidative‐nitrosative stress play a key role in placental infection by Trypanosoma cruzi

Nitric oxide synthase and oxidative‐nitrosative stress play a key role in placental infection by Trypanosoma cruzi

Chagas Disease Diagnostic Applications

Increases in [IP3]i aggravates diastolic [Ca2+] and contractile dysfunction in Chagas’ human cardiomyocytes

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