Ros-Lucas Albert, Gabaldón-Figueira Juan Carlos, Martínez-Peinado Nieves, Losada-Galván Irene, Posada Elizabeth, Escabia Elisa, Martín-Mur Beatriz, Gut Marta, Esteve-Codina Anna, Gascón Joaquim, Pinazo María-Jesús, Alonso-Padilla Julio
ISGlobal, Barcelona, Spain.
Universitat Pompeu Fabra, Barcelona, Spain.
J Infect Dis. 2024 Dec 16;230(6):1518-1528. doi: 10.1093/infdis/jiae429.
Chagas disease is a neglected tropical infection that affects millions of people. This study explores transcriptomic changes in Trypanosoma cruzi-infected subjects before and after treatment. Using total RNA sequencing, gene transcription was analyzed in peripheral blood mononuclear cells from asymptomatic (n = 19) and symptomatic (n = 8) T. cruzi-infected individuals, and noninfected controls (n = 15). Differential expression was compared across groups, and before/after treatment in infected subgroups. Untreated infection showed 12 upregulated and 206 downregulated genes in all T. cruzi-infected subjects, and 47 upregulated and 215 downregulated genes in the symptomatic group. Few differentially expressed genes were found after treatment and between the different infected groups. Gene set enrichment analysis highlighted immune-related pathways activated during infection, with therapy normalizing immune function. Changes in the kynurenine to tryptophan ratio, increased pretreatment, suggested chronic immune fatigue, which was restored posttreatment. These differentially expressed genes offer insights for potential biomarkers and pathways associated with disease progression and treatment response.
恰加斯病是一种被忽视的热带感染病，影响着数百万人。本研究探讨了克氏锥虫感染患者治疗前后的转录组变化。利用全RNA测序，对无症状（n = 19）和有症状（n = 8）的克氏锥虫感染个体以及未感染对照（n = 15）的外周血单核细胞中的基因转录进行了分析。比较了各组之间以及感染亚组治疗前后的差异表达情况。未经治疗的感染在所有克氏锥虫感染患者中显示12个基因上调和206个基因下调，在有症状组中显示47个基因上调和215个基因下调。治疗后以及不同感染组之间发现的差异表达基因很少。基因集富集分析突出了感染期间激活的免疫相关途径，治疗使免疫功能恢复正常。犬尿氨酸与色氨酸比值在治疗前升高，提示慢性免疫疲劳，治疗后恢复。这些差异表达基因可为与疾病进展和治疗反应相关的潜在生物标志物和途径提供见解。
