Phenotypic and Functional Signatures of Peripheral Blood and Spleen Compartments of Cynomolgus Macaques Infected With T. cruzi: Associations With Cardiac Histopathological Characteristics

Sathler-Avelar, Renato; Vitelli-Avelar, Danielle Marquete; Mattoso-Barbosa, Armanda Moreira; Pascoal-Xavier, Marcelo Antônio; Elói-Santos, Silvana Maria; Costa-Rocha, Ismael Artur da; Teixeira-Carvalho, Andréa; Dick, Edward J.; VandeBerg, Jane F.; VandeBerg, John L.; Martins‐Filho, Olindo Assis

doi:10.3389/fcimb.2021.701930

Cited by 3 publications

(2 citation statements)

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“…These characteristics are similar to those of Chagas disease in humans. The myocardium, muscle fibers, or esophagus may also be affected and may accompanied by arrythmia or esophageal dilatation 181 , 182 , 183 , 184 , 185 , 186 .…”

Section: Parasitic Infectionsmentioning

confidence: 99%

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Ohta

2023

J Toxicol Pathol

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Nonhuman primates (NHPs), which have many advantages in scientific research and are often the only relevant animals to use in assessing the safety profiles and biological or pharmacological effects of drug candidates, including biologics. In scientific or developmental experiments, the immune systems of animals can be spontaneously compromised possibly due to background infection, experimental procedure-associated stress, poor physical condition, or intended or unintended mechanisms of action of test articles. Under these circumstances, background, incidental, or opportunistic infections can seriously can significantly complicate the interpretation of research results and findings and consequently affect experimental conclusions. Pathologists and toxicologists must understand the clinical manifestations and pathologic features of infectious diseases and the effects of these diseases on animal physiology and experimental results in addition to the spectrum of infectious diseases in healthy NHP colonies. This review provides an overview of the clinical and pathologic characteristics of common viral, bacterial, fungal, and parasitic infectious diseases in NHPs, especially macaque monkeys, as well as methods for definitive diagnosis of these diseases. Opportunistic infections that can occur in the laboratory setting have also been addressed in this review with examples of cases of infection disease manifestation that was observed or influenced during safety assessment studies or under experimental conditions.

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Section: Parasitic Infectionsmentioning

confidence: 99%

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Ohta

2023

J Toxicol Pathol

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“…An ineffective immunological response can exacerbate the parasitic burden and incite an overwhelming inflammatory response, leading to tissue damage ( 43 ). Conversely, in the case of an effective immune response, the parasitic load and the inflammatory consequences are minimized ( 44 ).…”

Section: Discussionmentioning

confidence: 99%

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Vale,

Almeida,

Rimkute

et al. 2024

Front. Immunol.

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IntroductionChagas disease is a neglected parasitic disease caused by Trypanosoma cruzi. While most patients are asymptomatic, around 30% develop Chronic Chagasic Cardiomyopathy (CCC).MethodsHere, we employed high-dimensional flow cytometry to analyze CD4+ T and B cell compartments in patients during the chronic phase of Chagas disease, presenting the asymptomatic and mild or moderate/severe cardiac clinical forms.ResultsEffector CD27-CD4+ T cells were expanded in both CCC groups, and only mild CCC patients showed higher frequencies of effector memory and T follicular helper (Tfh) cells than healthy donors (CTL) and asymptomatic patients. Unsupervised analysis confirmed these findings and further revealed the expansion of a specific subpopulation composed of Tfh, transitional, and central memory CD4+ T cells bearing a phenotype associated with strong activation, differentiation, and exhaustion in patients with mild but not moderate/severe CCC. In contrast, patients with mild and moderate/severe CCC had lower frequencies of CD4+ T cells expressing lower levels of activation markers, suggesting resting status, than CTL. Regarding the B cell compartment, no alterations were found in naïve CD21-, memory cells expressing IgM or IgD, marginal zone, and plasma cells in patients with Chagas disease. However, expansion of class-switched activated and atypical memory B cells was observed in all clinical forms, and more substantially in mild CCC patients.DiscussionTaken together, our results showed that T. cruzi infection triggers changes in CD4+ T and B cell compartments that are more pronounced in the mild CCC clinical form, suggesting an orchestrated cellular communication during Chagas disease.ConclusionOverall, these findings reinforce the heterogeneity and complexity of the immune response in patients with chronic Chagas disease and may provide new insights into disease pathology and potential markers to guide clinical decisions.

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Animal models for exploring Chagas disease pathogenesis and supporting drug discovery

Khan,

Taylor,

Fortes Francisco

et al. 2024

Clin Microbiol Rev

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SUMMARY Infections with the parasitic protozoan Trypanosoma cruzi cause Chagas disease, which results in serious cardiac and/or digestive pathology in 30%–40% of individuals. However, symptomatic disease can take decades to become apparent, and there is a broad spectrum of possible outcomes. The complex and long-term nature of this infection places a major constraint on the scope for experimental studies in humans. Accordingly, predictive animal models have been a mainstay of Chagas disease research. The resulting data have made major contributions to our understanding of parasite biology, immune responses, and disease pathogenesis and have provided a platform that informs and facilitates the global drug discovery effort. Here, we provide an overview of available animal models and illustrate how they have had a key impact across the field.

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Phenotypic and Functional Signatures of Peripheral Blood and Spleen Compartments of Cynomolgus Macaques Infected With T. cruzi: Associations With Cardiac Histopathological Characteristics

Cited by 3 publications

References 44 publications

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Pathologic characteristics of infectious diseases in macaque monkeys used in biomedical and toxicologic studies

Signatures of CD4+ T and B cells are associated with distinct stages of chronic chagasic cardiomyopathy

Animal models for exploring Chagas disease pathogenesis and supporting drug discovery

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