在实验性克氏锥虫感染期间，IL-33/ST2信号通过协调血管监测和免疫调节回路维持肝肠稳态
IL-33/ST2 Signaling Sustains Hepato-Intestinal Homeostasis by Orchestrating Vascular Surveillance and Immune Regulatory Circuits During Experimental Trypanosoma cruzi Infection.
摘要(中文译文)
恰加斯病由克氏锥虫（Trypanosoma cruzi）引起，其特征是寄生虫持续存在与宿主驱动的免疫病理之间复杂的相互作用。尽管已知IL-33/ST2轴可调控2型免疫和组织修复，但其在慢性感染期间对组织稳态的贡献仍知之甚少。我们使用ST2缺陷型（ST2）和野生型BALB/c小鼠，随访至感染后100天，研究了IL-33/ST2信号在协调肝肠反应和全身免疫中的作用。ST2缺陷诱导了协调的全身性紊乱，包括血小板扩增和高白蛋白血症。在组织水平，ST2缺失加剧了肝脏炎症和纤维化重塑。在结肠中，ST2小鼠显示一氧化氮产生增加和寄生虫清除增强，但出现了明显的结构改变。我们的发现表明，IL-33/ST2信号与调控性程序相关。ST2缺陷与巡逻单核细胞减少相关，提示稳态内皮监测受损。这一特征还伴随炎症性单核细胞来源树突状细胞分化和巨噬细胞调控活性降低。这种改变的特征与IL-12驱动的Th1和细胞毒性T细胞反应增强相关，同时损害了IL-10相关的调控微环境，导致多器官炎症。这些发现表明，IL-33/ST2信号可能有助于克氏锥虫感染期间的免疫调控平衡，并将该轴确定为未来机制和治疗研究的候选通路。
Abstract
Chagas disease, caused by Trypanosoma cruzi, is characterized by a complex interplay between parasite persistence and host-driven immunopathology. Although the IL-33/ST2 axis is known to regulate type 2 immunity and tissue repair, its contribution to tissue homeostasis during chronic infection remains poorly understood. Using ST2-deficient (ST2) and wild-type BALB/c mice followed for up to 100 days postinfection, we investigated the role of IL-33/ST2 signaling in coordinating hepato-intestinal response and systemic immunity. ST2 deficiency induced coordinated systemic disturbances, including platelet expansion and hyperalbuminemia. At the tissue level, loss of ST2 exacerbated hepatic inflammation and fibrotic remodeling. In the colon, ST2 mice displayed increased nitric oxide production and enhanced parasite clearance, but developed marked structural alterations. Our findings suggest that IL-33/ST2 signaling is associated with regulatory programs. ST2 deficiency was associated with a reduction in patrolling monocytes, suggesting impaired homeostatic endothelial monitoring. This profile also coincided with inflammatory monocyte-derived dendritic cell differentiation and lowered macrophage regulatory activity. This altered profile was associated with amplified IL-12-driven Th1 and cytotoxic T-cell responses while impairing IL-10-associated regulatory niches, resulting in multiorgan inflammation. These findings suggest that IL-33/ST2 signaling may contribute to immunoregulatory balance during T. cruzi infection and identify this axis as a candidate pathway for future mechanistic and therapeutic investigation.
如何引用
AMA
Marcelo Eduardo Cardozo, Tatyane Martins Cirilo, José Bryan da Rocha Rihs, Jorge Lucas Nascimento Souza, Isabela de Brito Duval, Ana Rafaela Antunes-Porto, et al. IL-33/ST2 Signaling Sustains Hepato-Intestinal Homeostasis by Orchestrating Vascular Surveillance and Immune Regulatory Circuits During Experimental Trypanosoma cruzi Infection.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2026; doi:10.1096/fj.202600565RR.
APA
Marcelo Eduardo Cardozo, Tatyane Martins Cirilo, José Bryan da Rocha Rihs, Jorge Lucas Nascimento Souza, Isabela de Brito Duval, Ana Rafaela Antunes-Porto, et al (2026). IL-33/ST2 Signaling Sustains Hepato-Intestinal Homeostasis by Orchestrating Vascular Surveillance and Immune Regulatory Circuits During Experimental Trypanosoma cruzi Infection.. FASEB journal : official publication of the Federation of American Societies for Experimental Biology. https://doi.org/10.1096/fj.202600565RR
GB/T 7714
Marcelo Eduardo Cardozo, Tatyane Martins Cirilo, José Bryan da Rocha Rihs, Jorge Lucas Nascimento Souza, Isabela de Brito Duval, Ana Rafaela Antunes-Porto, et al. IL-33/ST2 Signaling Sustains Hepato-Intestinal Homeostasis by Orchestrating Vascular Surveillance and Immune Regulatory Circuits During Experimental Trypanosoma cruzi Infection.[J]. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2026 doi:10.1096/fj.202600565RR.
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