The Journal of infectious diseases · 2025
Single-Cell Targeted Transcriptomics Reveals Subset-Specific Immune Signatures Differentiating Asymptomatic and Cardiac Patients With Chronic Chagas Disease.
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Souza-Silva Thaiany G, Figueiredo Amanda, Morais Katia L P, Apostólico Juliana, Pantaleao Alexandre, Mutarelli Antônio, Araújo Silvana Silva, Nunes Maria do Carmo Pereira, Gollob Kenneth J, Dutra Walderez O
Аннотация
BACKGROUND: Human infection with Trypanosoma cruzi leads to Chagas disease, which induces profound changes in the immune response across different cell subsets, influencing parasite control and disease pathology. Dissecting the functional characteristics of distinct immune cells in patients with the asymptomatic (indeterminate, IND) or the cardiac (CCC) clinical forms is crucial for unveiling mechanisms of disease progression and pathology, and identifying disease markers.
METHODS: Immune-gene targeted single-cell RNA sequencing was applied to peripheral blood mononuclear cells obtained from patients with IND and CCC to unravel the immune landscape in these polar, well-characterized, clinical groups.
RESULTS: Our findings revealed different myeloid and lymphoid cell clusters in the cohorts, each exhibiting unique gene expression patterns. CCC was characterized by an increased frequency of KLRB1+CD4+, TBX21+CD8+ T cells, and NK cells, which exhibited upregulation of genes associated with cytotoxic and apoptotic responses. Furthermore, we observed monocyte, B-cell subsets, along with dendritic cells, expressing inflammatory and notably cytotoxic genes.
CONCLUSIONS: These results reveal cell-specific changes in patients with CCC compared to IND chronic Chagas disease, highlighted by distinct gene expression patterns. These nuanced changes indicate an immune signature linked to the clinical forms of chronic Chagas disease, which provide information regarding disease pathology, indicating potential markers related to the disease progression.
METHODS: Immune-gene targeted single-cell RNA sequencing was applied to peripheral blood mononuclear cells obtained from patients with IND and CCC to unravel the immune landscape in these polar, well-characterized, clinical groups.
RESULTS: Our findings revealed different myeloid and lymphoid cell clusters in the cohorts, each exhibiting unique gene expression patterns. CCC was characterized by an increased frequency of KLRB1+CD4+, TBX21+CD8+ T cells, and NK cells, which exhibited upregulation of genes associated with cytotoxic and apoptotic responses. Furthermore, we observed monocyte, B-cell subsets, along with dendritic cells, expressing inflammatory and notably cytotoxic genes.
CONCLUSIONS: These results reveal cell-specific changes in patients with CCC compared to IND chronic Chagas disease, highlighted by distinct gene expression patterns. These nuanced changes indicate an immune signature linked to the clinical forms of chronic Chagas disease, which provide information regarding disease pathology, indicating potential markers related to the disease progression.