Braga Yarlla Loyane Lira, do Carmo Neto José Rodrigues, Franco Pablo Igor Ribeiro, de Oliveira Jordana Fernandes, Trevisan Rafael Obata, de Vito Fernanda Bernadelli, de Oliveira Flávia Aparecida, Celes Mara Rúbia Nunes, da Silva Marcos Vinícius, Machado Juliana Reis
Department of Bioscience and Technology, Institute of Tropical Pathology and Public Health, Federal University of Goiás, Goiânia, GO, 74605-450, Brazil.
General Pathology, Federal University of Triângulo Mineiro, Uberaba, Minas Gerais, Brazil.
Inflammation. 2025 Sep 12. doi: 10.1007/s10753-025-02322-4.
Chagas disease (CD), caused by Trypanosoma cruzi, leads to cardiomyopathy in approximately 20-30% of infected individuals. Interleukin-11 (IL-11) has been implicated in cardiac fibrosis, although its immunological role in this context remains unclear. This study investigated the temporal dynamics of IL-11 and its receptor, IL-11Rα, expression in the hearts of C57BL/6 mice infected with 1,000 trypomastigote forms of the Y or Colombian strains of T. cruzi. Mice were euthanized at 5, 15, 30, 60, and 120 days post-infection (dpi). Survival, parasitemia, and body and heart weights were monitored. Cardiac tissue was analyzed for parasite nests, myocarditis, collagen deposition, and expression of the IL-11 receptor alpha (IL-11Rα). Cytokine profiles were evaluated by ELISA and Cytometric Bead Array. Histopathological analysis revealed more intense myocarditis, parasite load, and collagen deposition in mice infected with the Colombian strain. Both strains induced IFN-γ, TNF-α, and IL-6 in cardiac tissue; however, IL-10, IL-4, and IL-17 were detected only in the Y strain, indicating a more balanced immune response. Despite the absence of significant IL-11 upregulation in either infection, IL-11Rα expression was progressively increased over time and positively correlated with collagen deposition. These findings suggest that IL-11Rα may play a role in cardiac remodeling and fibrosis independently of IL-11 upregulation. The results reinforce the importance of T. cruzi strain variability in disease outcome and highlight the IL-11/IL-11Rα axis as a potential target for further investigation in Chagas cardiomyopathy.
恰加斯病（CD）由克氏锥虫引起，约20%-30%的感染者会发展为心肌病。白细胞介素-11（IL-11）与心脏纤维化有关，但其在这种情况下的免疫作用尚不清楚。本研究调查了感染1000个克氏锥虫Y株或哥伦比亚株的锥鞭毛体形式的C57BL/6小鼠心脏中IL-11及其受体IL-11Rα表达的时间动态。在感染后5、15、30、60和120天对小鼠实施安乐死。监测生存率、寄生虫血症以及体重和心脏重量。分析心脏组织中的寄生虫巢、心肌炎、胶原沉积以及白细胞介素-11受体α（IL-11Rα）的表达。通过酶联免疫吸附测定（ELISA）和细胞计数微珠阵列评估细胞因子谱。组织病理学分析显示，感染哥伦比亚株的小鼠心肌炎、寄生虫负荷和胶原沉积更为严重。两种菌株均在心脏组织中诱导产生干扰素-γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）；然而，仅在Y株中检测到白细胞介素-10（IL-10）、白细胞介素-4（IL-4）和白细胞介素-17（IL-17），表明免疫反应更为平衡。尽管在任何一种感染中均未出现显著的IL-11上调，但IL-11Rα表达随时间逐渐增加，且与胶原沉积呈正相关。这些发现表明，IL-11Rα可能在心脏重塑和纤维化中发挥作用，而与IL-11上调无关。结果强化了克氏锥虫菌株变异性在疾病结局中的重要性，并突出了IL-11/IL-11Rα轴作为恰加斯心肌病进一步研究的潜在靶点。
