IL-33/ST2 Signaling Protects the Heart by Restraining Inflammation and Parasite Burden during Trypanosoma cruzi Experimental Infection

作者：Marcelo Eduardo Cardozo, Tatyane Martins Cirilo, Jorge Lucas Nascimento Souza, José Bryan da Rocha Rihs, Isabela de Brito Duval, Fernando Bento Rodrigues Oliveira, Mayra Fernanda Ricci, Laura Lis de Oliveira Santos, Livia Fernanda Santana, Luís Silva, Chiara Cássia Oliveira Amorim, Ana Rafaela Antunes-Porto, Idam de Oliveira‐Junior, Ana Laura Grossi de Oliveira, Leslie Amaral, Gabriela Lemos, G Silva, Ivan Lobo de Sousa Marques, Marina Possa dos Reys, Geovanni Dantas Cassali, Artur Santos‐Miranda, Luísa Mourão Dias Magalhães, Lilian Lacerda Bueno, Fabiana S. Machado, Ricardo Toshio Fujiwara · 发表于：ACS Infectious Diseases · 年份：2025 · DOI：10.1021/acsinfecdis.5c00859 · 被引用次数：3 · 研究领域：IL-33, ST2, and ILC Pathways、Trypanosoma species research and implications、Immune Cell Function and Interaction

High Resolution Image Download MS PowerPoint Slide Chagas disease (CD), caused by the parasite Trypanosoma cruzi, affects millions of people worldwide and often leads to fatal heart damage. The course of CD is influenced by how the immune system is tuned, which can protect the host and favor parasite persistence. Interleukin-33 (IL-33) is an alarmin released upon tissue injury that signals through the ST2 receptor, exerting context-dependent regulatory or pathogenic effects. However, the role of the IL-33/ST2 axis in T. cruzi -induced myocarditis remains unclear. Here, using ST2-deficient (ST2 –/– ) and wild-type (WT) female mice infected with the T. cruzi Y strain, we investigated its contribution to cardiac inflammation, tissue damage, and parasite burden. We found that ST2 signaling was not essential for controlling parasitemia, but its deficiency led to early onset myocarditis, disorganized fibrosis, and distinct electrical conduction. This severe immunopathology was driven by a remodeling of the cardiac immune landscape, with ST2 –/– mice exhibiting an influx of IFN-γ-producing monocytes and a shift in resident and monocyte-derived macrophages toward a pathogenic, pro-inflammatory phenotype. Likewise, the cardiac T cell compartment, including both conventional and γδ T cells, was skewed toward an inflammatory, IFN-γ-driven profile. However, infected ST2-deficient mice also displayed higher cardiac parasite burden and impaired nitric oxide production, indicating a dysfunc...