Chagas cardiomyopathy is associated with a high susceptibility to T. cruzi infection in monocyte-derived macrophages and a predominance of CD4+CD45RO+ T-cells with immunoregulatory patterns

Carvalho, Ana Maria Ravena Severino; Ferraz, Isabela de Andrade; Hojo-Souza, Natália Satchiko; Medeiros, Fernanda Alvarenga Cardoso; Viana, Laila Almeida; Bartholomeu, Daniella Castanheira; Chaves, Ana Cristina; Souza, Thiago M. de; Silva, Matheus Fernandes Costa e; Mendes, Tiago; Duarte, Mariana C.; Rocha, Manoel Otávio da Costa; Menezes‐Souza, Daniel

doi:10.1016/j.actatropica.2022.106749

Cited by 1 publication

(1 citation statement)

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“…In this sense, it has been reported that stimulating T-cells from cardiac patients alongside T. cruzi trypomastigotes results in a prevailing regulatory response rather than a type 1 response, as evidenced by elevated IL-10 production and decreased levels of IFN-γ and IFN-γ/IL-10 ratio . Likewise, although it has been reported that IL-10 is required for macrophage M2 polarization, our results suggest that while an increase in IL-10 could be necessary, it is not sufficient to upregulate FIZZ, Ym1, CD206 and PPARα mRNA in infected mice.…”

Section: Discussionsupporting

confidence: 92%

Fenofibrate Induces a Resolving Profile in Heart Macrophage Subsets and Attenuates Acute Chagas Myocarditis

Ruiz Luque,

Cevey,

Pieralisi

et al. 2024

ACS Infect. Dis.

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Chagas disease, caused by Trypanosoma cruzi, stands as the primary cause of dilated cardiomyopathy in the Americas. Macrophages play a crucial role in the heart's response to infection. Given their functional and phenotypic adaptability, manipulating specific macrophage subsets could be vital in aiding essential cardiovascular functions including tissue repair and defense against infection. PPARα are ligand-dependent transcription factors involved in lipid metabolism and inflammation regulation. However, the role of fenofibrate, a PPARα ligand, in the activation profile of cardiac macrophages as well as its effect on the early inflammatory and fibrotic response in the heart remains unexplored. The present study demonstrates that fenofibrate significantly reduces not only the serum activity of tissue damage biomarker enzymes (LDH and GOT) but also the circulating proportions of pro-inflammatory monocytes (CD11b + LY6C high ). Furthermore, both CD11b + Ly6C low F4/80 high macrophages (MΦ) and recently differentiated CD11b + Ly6C high F4/80 high monocyte-derived macrophages (MdMΦ) shift toward a resolving phenotype (CD206 high ) in the hearts of fenofibrate-treated mice. This shift correlates with a reduction in fibrosis, inflammation, and restoration of ventricular function in the early stages of Chagas disease. These findings encourage the repositioning of fenofibrate as a potential ancillary immunotherapy adjunct to antiparasitic drugs, addressing inflammation to mitigate Chagas disease symptoms.

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Section: Discussionsupporting

confidence: 92%