The role of CCR5 in Chagas disease - a systematic review

Oliveira, Amanda Priscila de; Ayo, Christiane Maria; Bestetti, Reinaldo B.; Mattos, Cinara Cássia Brandão de; Cavasini, Carlos Eugênio

doi:10.1016/j.meegid.2016.08.012

Cited by 17 publications

(15 citation statements)

References 54 publications

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“…32,33 Studies have shown that T. cruzi infection triggers an increase in the expression of chemokine receptors in T cells and their ligands; however, whether and how these immune mediators might induce or control deleterious effector functions during Chagas disease are still unclear, mainly in the chronic phase. [34][35][36] Our data demonstrate that T. cruzi induces the production of type 1 chemokines. As a chronic inflammatory process, T. cruzi infection induces changes in the naive/effector/memory T cell compartments in humans.…”

Section: Discussionmentioning

confidence: 55%

“…T cells have been shown to play an important role both in the control of several parasite infections and in the induction of immunopathology . Studies have shown that T. cruzi infection triggers an increase in the expression of chemokine receptors in T cells and their ligands; however, whether and how these immune mediators might induce or control deleterious effector functions during Chagas disease are still unclear, mainly in the chronic phase . Our data demonstrate that T. cruzi induces the production of type 1 chemokines.…”

Section: Discussionmentioning

confidence: 62%

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Increased frequencies of circulating CCR5+ memory T cells are correlated to chronic chagasic cardiomyopathy progression

Roffê

Santos

et al. 2019

Journal of Leukocyte Biology

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The infection with the protozoan parasite Trypanosoma cruzi causes Chagas disease, a neglected tropical disease in Latin America and an imported emerging disease worldwide. Chronic Chagasic cardiomyopathy (CCC), a progressive inflammatory and fibrosing disease, is the most prominent clinical form of Chagas disease, culminating in heart failure and high rates of sudden death. CCC pathogenesis is influenced by both host and parasite factors and is proposed to be mostly immune‐driven. Chemokines are crucial players in orchestrating immune cell recruitment to infected tissues and inflammation. Herein, we investigated inflammatory chemokine receptor expression on circulating T cells in patients stratified by CCC severity. Compared to asymptomatic individuals, we found increased percentages of effector CD4+ T cells and central memory CD4+ and CD8+ T cells expressing CCR5 in patients with structural cardiopathy, but normal global ventricular function and no symptoms of chronic heart failure. Even naïve T cells expressed CCR5 in these patients. In contrast, reduced frequencies of CD4+ and CD8+ effector T cells expressing CXCR3 were observed in patients presenting with severe heart disease. Patients with increased left ventricular diameter, heart enlargement, and insufficiency had higher frequencies of CCR5+ effector and effector memory CD8+ T cells. Moreover, the percentage of effector CCR5+ CD8+ T cells was increased in patients with a reduced ejection fraction. Our results show that high expression CCR5 and low expression of CXCR3 on circulating T cells are associated with worse prognosis, possibly reflecting immune‐mediated cardiac remodeling of CCC.

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Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 62%

Increased frequencies of circulating CCR5+ memory T cells are correlated to chronic chagasic cardiomyopathy progression

Roffê

Santos

et al. 2019

Journal of Leukocyte Biology

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“…Although inflammation is important to limit parasite action on the host, in general, an inflammatory environment facilitates the establishment and progression of Chagas heart disease. In addition, Trypanosoma ‐related factors and human genetics also have a critical impact on the different manifestations of Chagas disease (Ayo et al, 2013; Oliveira et al, 2016; Pérez‐Molina & Molina, 2018; Vasconcelos, Montenegro, Azevedo, Gomes, & Morais, 2012). Looking at host genetics, HLA alleles and variants in cytokine genes impact both resistance and susceptibility to Chagas diseases and the associated health problems (Ayo et al, 2013; Vasconcelos et al, 2012).…”

Section: Ccr5 and Ccr5δ32 In Parasitic Infectionsmentioning

confidence: 99%

“…Moreover, a body of evidence supports the involvement of the CCR5 protein (Batista et al, 2018; Dutra, Rocha, & Teixeira, 2005; Hardison et al, 2006; Kroll‐Palhares et al, 2008; Machado et al, 2005; Marino et al, 2005; Medeiros et al, 2009; Roffe et al, 2019; Roffê et al, 2010; Silva et al, 2007), as well as gene variants of CCR5 and CCR5 ligands (Batista et al, 2018; Calzada et al, 2001; Flórez et al, 2012; Machuca et al, 2014; Oliveira et al, 2015, 2016) on varied aspects of Chagas disease, mainly associated to the development of Chagas heart disease. For example, animal‐based evidence pointed to a protective role of CCR5 in controlling T. cruzi replication and maintaining a protective immune response in acute infection (Hardison et al, 2006).…”

Section: Ccr5 and Ccr5δ32 In Parasitic Infectionsmentioning

confidence: 99%

“…Many CCR5 variants were already addressed in viral, bacterial and parasitic infections, and some have a notorious role in particular outcomes. For example, in Trypanosoma cruzi infection, several CCR5 polymorphisms (rs333, rs3176763, rs11575815, rs1799988, rs1800024, rs2856758) were associated to differential clinical outcomes (Batista et al, 2018; Calzada, Nieto, Beraún, & Martín, 2001; Flórez, Martín, & González, 2012; Frade et al, 2013; Machuca, Suárez, Echeverría, Martín, & González, 2014; Nogueira et al, 2012; Oliveira et al, 2015, 2016). Recently, a genetic variant similar to CCR5Δ32, called CCR5Δ24, has been associated with HIV protection in the African population (Arendt et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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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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Determination of the Th1, Th2, Th17, and Treg cytokine profile in patients with chronic Chagas heart disease and systemic arterial hypertension

Bestetti

Dellalibera-Joviliano

Lopes

et al. 2018

Heart Vessels

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Chronic Chagas heart disease (CCHD affects about 30% of patients with chronic Chagas disease (CCD). Systemic arterial hypertension (SAH) afflicts about 25% of patients with CCD. The association of CCHD with SAH (CCHD-SAH) predisposes patients to develop chronic heart failure. The role of cytokines in disease progression in patients with CCHD-SAH is unknown. Accordingly, the aim of this study was to evaluate the plasma levels of cytokines expressing the Th1, Th2, Th17 pattern, as well as Treg cytokines, TNF-alpha, IL-1β, IL-8, IL-7 in patients with SAH-CCHD to get insight into the immunomodulation process in patients with this condition. Fifteen patients with CCHD, 22 patients with CCHD-SAH, and 28 controls were studied. All patients underwent history-taking, physical examination, 12-lead resting ECG, chest X-ray, and Doppler-echocardiogram. Ten of 15 (66%) patients with CCHD, and 16 of 22 (73%) patients with CCHD-SAH had decreased left ventricular ejection fraction (p > 0.05). Cytokines levels were performed on plasma samples using the ELISA method. Overall, proinflammatory, anti-inflammatory, and regulatory cytokine levels were increased in patients with CCHD-SAH in comparison to patients with CCHD and controls. However, such a difference was higher regarding IL-2, IL-5, IL-17, IL-12, and TNF-alpha cytokine levels, respectively. Cytokine levels were higher in CCHD patients in comparison to controls. Patients with CCHD-SAH have increased plasma levels of pro-inflammatory, anti-inflammatory, and regulatory cytokines in comparison with CCHD patients, thus suggesting a higher level of immunomodulation in patients with CCHD-SAH.

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The role of CCR5 in Chagas disease - a systematic review

Cited by 17 publications

References 54 publications

Increased frequencies of circulating CCR5+ memory T cells are correlated to chronic chagasic cardiomyopathy progression

Increased frequencies of circulating CCR5+ memory T cells are correlated to chronic chagasic cardiomyopathy progression

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

Determination of the Th1, Th2, Th17, and Treg cytokine profile in patients with chronic Chagas heart disease and systemic arterial hypertension

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