Distinct Treatment Outcomes of Antiparasitic Therapy in Trypanosoma cruzi-Infected Children Is Associated With Early Changes in Cytokines, Chemokines, and T-Cell Phenotypes

Albareda, María Cecilia; Natale, María A.; Rissio, Ana María De; Fernández, Marisa; Serjan, Alicia; Alvarez, M; Cooley, Gretchen; Shen, Huifeng; Viotti, Rodolfo; Búa, Jacqueline; Eiro, Melisa D. Castro; Núñez, Myriam; Fichera, Laura E.; Lococo, Bruno; Scollo, Karenina; Tarleton, Rick L.; Laucella, Susana A.

doi:10.3389/fimmu.2018.01958

Cited by 25 publications

(28 citation statements)

References 32 publications

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“…Indeed, we showed negative correlation between reduced percentage of naive CD4 + and CD8 + T cells and severity of cardiac Chagas disease and between naïve CD4 + T cells and the diameter of the LV. In this way, antiparasitic therapy in patients with Chagas disease restored the levels of total naive (CD45RA + CCR7 + CD62L + ) CD4 + and CD8 + T cells and decreased the percentage of total effector CD4 + T cells to values similar to those of uninfected subjects after 24 months . So, the expression of CCR7 seems to be inversely correlated to severity of disease.…”

Section: Discussionmentioning

confidence: 82%

“…CD4 + and CD8 + T cells 38 and decreased the percentage of total effector CD4 + T cells to values similar to those of uninfected subjects after 24 months. 39 So, the expression of CCR7 seems to be inversely correlated to severity of disease. Moreover, the frequencies of EM and CM CD4 + and CD8 + T cell subpopulations are increased in patients with CCC in comparison to indeterminate patients, being CM CD4 + and CD8 + T cells directly correlated to severity of CCC.…”

Section: F I G U R E 7 Severity Of Chronic Chagasic Cardiomyopathy Comentioning

confidence: 99%

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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: 82%

Section: F I G U R E 7 Severity Of Chronic Chagasic Cardiomyopathy Comentioning

confidence: 99%

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 quality of T-cell responses might be a key factor, not only in disease evolution but also in chemotherapy responsiveness [137]. This may also explain the differing response rate to anti-parasitic treatment among children in comparison with adults, as children have a T-cell profile associated with a more robust clinical response [138]. Additionally, animal model research demonstrates that a small proportion of trypomastigotes are dormant at any given time during infection, and are likely to be protected from anti-parasitic compounds in this state [139].…”

Section: Why Are There Poor Cure Rates In Chronic Patients?mentioning

confidence: 99%

WHF IASC Roadmap on Chagas Disease

Echeverría

Marcus

Novick

et al. 2020

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Background: Chagas Disease is a neglected tropical disease caused by the protozoan Trypanosoma cruzi, with some of the most serious manifestations affecting the cardiovascular system. It is a chronic, stigmatizing condition, closely associated with poverty and affecting close to 6 million people globally. Although historically the disease was limited to endemic areas of Latin America recent years have seen an increasing global spread. In addition to the morbidity and mortality associated with the disease, the social and economic burdens on individuals and society are substantial. Often called the 'silent killer', Chagas disease is characterized by a long, asymptomatic phase in affected indivi duals. A pproximately 30% then go on develop chronic Chagas cardiomyopathy and other serious cardiac complications such as stroke, rhythm disturbances and severe heart failure. Methods: In a collaboration of the World Hearth Federation (WHF) and the Inter-American S ociety of Cardiology (IASC) a writing group consisting of 20 diverse experts on Chagas disease (CD) was convened. The group provided up to date expert knowledge based on their area of expertise. An extensive review of the literature describing obstacles to diagnosis and treatment Echeverría et al: WHF IASC Roadmap on Chagas Disease Art. 26, page 2 of 31 of CD along with proposed solutions was conducted. A survey was sent to all WHF Members and, using snowball sampling to widen the consultation, to a variety of health care professionals working in the CD global health community. The results were analyzed, open comments were reviewed and consolidated, and the findings were incorporated into this document, thus ensuring a consensus representation. Results: The WHF IASC Roadmap on Chagas Disease offers a comprehensive summary of current knowledge on prevention, diagnosis and management of the disease. In providing an analysis of 'roadblocks' in access to comprehensive care for Chagas disease patients, the document serves as a framework from which strategies for implementation such as national plans can be formulated. Several dimensions are considered in the analysis: healthcare system capabilities, governance, financing, community awareness and advocacy. Conclusion: The WHF IASC Roadmap proposes strategies and evidence-based solutions for healthcare professionals, health authorities and governments to help overcome the barriers to comprehensive care for Chagas disease patients. This roadmap describes an ideal patient care pathway, and explores the roadblocks along the way, offering potential solutions based on available research and examples in practice. It represents a call to action to decision-makers and health care professionals to step up efforts to eradicate Chagas disease.

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“…Luminex-based assays excel at quantitative monitoring of changes in antibody levels over time (1)(2)(3)(4)(5)(6)(7). We analyzed temporal trends in levels of SARS-CoV-2-specific antibody binding for a subset of individuals following COVID-19 symptoms (Fig.…”

Section: Sars-cov-2mentioning

confidence: 99%

A flexible, pan-species, multi-antigen platform for the detection and monitoring of SARS-CoV-2-specific antibody responses

Shen

Forgacs

Chapla

et al. 2021

Preprint

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The SARS-CoV-2 pandemic and the vaccination effort that is ongoing has created an unmet need for accessible, affordable, flexible and precise platforms for monitoring the induction, specificity and maintenance of virus-specific immune responses. Herein we validate a multiplex (Luminex-based) assay capable of detecting SARS-CoV-2-specific antibodies irrespective of host species, antibody isotype, and specimen type (e.g. plasma, serum, saliva or blood spots). The well-established precision of Luminex-based assays provides the ability to follow changes in antibody levels over time to many antigens, including multiple permutations of the most common SARS-CoV-2 antigens. This platform can easily measure antibodies known to correlate with neutralization activity as well as multiple non-SARS-CoV-2 antigens such as vaccines (e.g. Tetanus toxoid) or those from frequently encountered agents (influenza), which serve as stable reference points for quantifying the changing SARS-specific responses. All of the antigens utilized in our study can be made in-house, many in E. coli using readily available plasmids. Commercially sourced antigens may also be incorporated and newly available antigen variants can be rapidly produced and integrated, making the platform adaptable to the evolving viral strains in this pandemic.Brief SummaryA multi-antigen assay for monitoring SARS-CoV-2-specific antibodies irrespective of host species, antibody isotype, and specimen type was developed.

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Distinct Treatment Outcomes of Antiparasitic Therapy in Trypanosoma cruzi-Infected Children Is Associated With Early Changes in Cytokines, Chemokines, and T-Cell Phenotypes

Cited by 25 publications

References 32 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

WHF IASC Roadmap on Chagas Disease

A flexible, pan-species, multi-antigen platform for the detection and monitoring of SARS-CoV-2-specific antibody responses

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