Natural killer (NK) cells with downregulated activating receptors and IL-10 production promote Trypanosoma cruzi T-cell responses in subjects in the Chronic phase of Trypanosoma cruzi infection: An exploratory immunological analysis
PLOS Neglected Tropical Diseases·
- DOI
- 10.1371/journal.pntd.0014622
- PMID
- —
- PMCID
- —
- OpenAlex
- W7202245304
- Study type
- Journal article
- Publisher
- Public Library of Science (PLoS)
- Article type
- journal-article
- Integrity
- current
Why this research matters now
The findings suggest NK cell dysregulation in chronic Chagas disease may contribute to cardiac pathology through uncontrolled cytotoxic responses against persistent parasites, while benznidazole treatment may help restore NK cell balance.
Structured evidence summary
Research question
The study investigates NK cell phenotype and function across severity stages of chronic Chagas cardiomyopathy, examines changes following benznidazole treatment, and evaluates associations between NK cell characteristics and T. cruzi-specific T-cell responses.
Study design
This was a cohort study of 51 subjects with chronic T. cruzi infection using high-dimensional flow cytometry with Boolean gating for NK cell phenotyping, along with ELISPOT assays measuring IFN-γ and IL-2 production from CD56/CD4/CD8-depleted PBMCs in response to T. cruzi antigens.
Population and setting
The study enrolled 51 subjects with chronic T. cruzi infection exhibiting varying degrees of heart disease severity, ranging from no cardiac involvement to advanced cardiomyopathy.
Main findings
Subjects with advanced cardiomyopathy showed increased NK cell counts expressing activating receptors (NKp46, CD16) and the differentiation marker CD57, with enrichment of polyfunctional cytotoxic NK cells (CD56+ CD107+ granzyme B+ TNF-α+) and depletion of IL-10-producing NK cells. Following benznidazole treatment, NK function shifted toward monofunctionality in subjects with declining T. cruzi antibodies. Depletion of CD56+ cells significantly reduced IFN-γ-producing cells in response to T. cruzi antigens.
Public-health relevance
The findings suggest NK cell dysregulation in chronic Chagas disease may contribute to cardiac pathology through uncontrolled cytotoxic responses against persistent parasites, while benznidazole treatment may help restore NK cell balance.
Important limitations
This summary is limited to the supplied single-article abstract and metadata; the original full text is required for comprehensive interpretation of study limitations, potential confounding factors, and clinical applicability.
GIDS interpretation
This immunological study characterizes NK cell dynamics in chronic Chagas cardiomyopathy and provides mechanistic context for understanding disease progression and treatment effects on cellular immunity.
Related GIDS surveillance
Literature context does not validate, explain, or change a surveillance signal. Exact and contextual relationships are shown separately.
Evidence relationships
This article has 5 auditable classifier relationships to diseases, places, topics, and study design.