Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

Ayo, Christiane Maria; Dalalio, Márcia Machado de Oliveira; Visentainer, Jeane Eliete Laguila; Reis, Pâmela Guimarães; Sippert, Emília; Jarduli, Luciana Ribeiro; Alves, Hugo Vicentin; Sell, Ana Maria

doi:10.1155/2013/284729

Cited by 49 publications

(42 citation statements)

References 135 publications

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“…This may be attributed in part to the genetic aspects and immune competence of local human populations (Ayo et al, 2013; Deng et al, 2013; Frade et al, 2013; Luz et al, 2016; Nogueira et al, 2012) and/or to parasite genetic heterogeneities. The latter hypothesis finds support in animal studies (that do not strictly recapitulate Chagas disease-associated physiopathologies), which revealed inter-strain variations in complex phenotypes such as parasitemia, virulence, tissue tropism/distribution and pathogenicity (Figure 1) (Andrade et al, 1999; Andrade, 1990; Camandaroba, Pinheiro Lima and Andrade, 2002; de Souza et al, 1996; Laurent et al, 1997; Monteiro et al, 2013; Revollo et al, 1998; Roellig et al, 2010).…”

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

confidence: 99%

“…The current consensus states that a failure to down-regulate the inflammatory response, which is maintained by parasite persistence in tissues, appears to play a predominant role. Other contributory factors include sex, age and genotypic features of the patient, route of infection, sustained vector exposure, auto-immune responses and the existence of co-infections (Ayo et al, 2013; Bonney and Engman, 2015; Deng et al, 2013; Frade et al, 2013; Luz et al, 2016; Machado et al, 2012; Nogueira et al, 2012; Tarleton, 2015; Teixeira et al, 2011). As mentioned, a possible role of parasite genotype on Chagas disease progression/outcome has been proposed, though further research supported by novel and robust epidemiologic and diagnostic tools, and appropriate animal models are needed to address this issue.…”

Section: Diagnostic Applications For Chagas D Isease: Present Knowledgementioning

confidence: 99%

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

confidence: 99%

Section: Diagnostic Applications For Chagas D Isease: Present Knowledgementioning

confidence: 99%

Chagas Disease Diagnostic Applications

Balouz

Agüero

Buscaglia

2017

Advances in Parasitology

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“…Of note, T. cruzi infection is a neglected tropical disease with critical social and economic impacts. Triatomine bugs are the main vectors of T. cruzi (Ayo et al, 2013; Pérez‐Molina & Molina, 2018). In brief, an individual becomes infected when metacyclic trypomastigotes of T. cruzi , found in faeces of an infected triatomine bug, penetrate the skin through lesions produced by the bug's oral apparatus following a blood meal on human skin.…”

Section: Ccr5 and Ccr5δ32 In Parasitic Infectionsmentioning

confidence: 99%

“…The parasite can also penetrate the host through mucosal membranes (Pérez‐Molina & Molina, 2018). Humans can also be infected by T. cruzi in other ways, including the ingestion of contaminated food and by congenital or sexual transmission (Ayo et al, 2013).…”

Section: Ccr5 and Ccr5δ32 In Parasitic Infectionsmentioning

confidence: 99%

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Ellwanger

Kaminski

Rodrigues

et al. 2020

Int J Immunogenetics

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The CCR5 molecule was reported in 1996 as the main HIV‐1 co‐receptor. In that same year, the CCR5Δ32 genetic variant was described as a strong protective factor against HIV‐1 infection. These findings led to extensive research regarding the CCR5, culminating in critical scientific advances, such as the development of CCR5 inhibitors for the treatment of HIV infection. Recently, the research landscape surrounding CCR5 has begun to change. Different research groups have realized that, since CCR5 has such important effects in the chemokine system, it could also affect other different physiological systems. Therefore, the effect of reduced CCR5 expression due to the presence of the CCR5Δ32 variant began to be further studied. Several studies have investigated the role of CCR5 and the impacts of CCR5Δ32 on autoimmune and inflammatory diseases, various types of cancer, and viral diseases. However, the role of CCR5 in diseases caused by bacteria and parasites is still poorly understood. Therefore, the aim of this article is to review the role of CCR5 and the effects of CCR5Δ32 on bacterial (brucellosis, osteomyelitis, pneumonia, tuberculosis and infection by Chlamydia trachomatis) and parasitic infections (toxoplasmosis, leishmaniasis, Chagas disease and schistosomiasis). Basic information about each of these infections was also addressed. The neglected role of CCR5 in fungal disease and emerging studies regarding the action of CCR5 on regulatory T cells are briefly covered in this review. Considering the “renaissance of CCR5 research,” this article is useful for updating researchers who develop studies involving CCR5 and CCR5Δ32 in different infectious diseases.

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“…However, one study performed in familial clusters in Brazil displayed evidence that genetic factors may influence both, seropositivity and cardiac outcome traits, and additional data showed that heritability were 0.56 . In line with this, several genetic variants of immune genes have been analyzed in endemic populations finding some associations to risk to infection and/or differential predisposition to the severity of Chagas disease . To date, only one genome wide association study (GWAS) has been performed on Chagasic patients; nevertheless, due to technical limitations there was not conclusive results indicating any association to severity of disease .…”

Section: Genotype and Allele Distribution Of Foxo3 Rs12212067 Polymormentioning

confidence: 99%

Analysis of association of FOXO3 gene with Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

Rodríguez

González

Martín

2016

HLA

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FOXO3, a member of the Forkhead family of proteins, plays a role in controlling immune response. FOXO3 gene variant rs12212067 has been associated to differential severity of infectious diseases like malaria. In this study, we assessed whether this FOXO3 gene polymorphism is related to susceptibility to infection by Trypanosoma cruzi and/or chronic Chagasic cardiomyopathy. A total of 1171 individuals from a Colombian region endemic for Chagas disease, classified as seronegative (n = 595), seropositive asymptomatic (n = 175) and chronic Chagasic cardiomyopathy (n = 401) were genotyped for the FOXO3 rs12212067 using TaqMan allelic discrimination. Our results showed no statistically significantly differences between allelic and genotypic frequencies of rs12212067 in seronegative individuals compared with seropositive individuals. Similarly, we observed no evidence of association when asymptomatic individuals were compared with chronic Chagasic cardiomyopathy patients. Our data suggest that the FOXO3 genetic variant rs12212067 do not play an important role in Chagas disease.

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Genetic Susceptibility to Chagas Disease: An Overview about the Infection and about the Association between Disease and the Immune Response Genes

Cited by 49 publications

References 135 publications

Chagas Disease Diagnostic Applications

Chagas Disease Diagnostic Applications

CCR5 and CCR5Δ32 in bacterial and parasitic infections: Thinking chemokine receptors outside the HIV box

Analysis of association of FOXO3 gene with Trypanosoma cruzi infection and chronic Chagasic cardiomyopathy

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