Association between altered tryptophan metabolism, plasma aryl hydrocarbon receptor agonists, and inflammatory Chagas disease

AMBROSIO, LAURA FERNANDA; VOLPINI, XIMENA; QUIROZ, JUAN NAHUEL; BRUGO, MARÍA BELÉN; KNUBEL, CAROLINA PAOLA; HERRERA, MELISA ROCÍO; FOZZATTI, LAURA; AVILA PACHECO, JULIÁN; CLISH, CLARY B.; TAKENAKA, MAISA C.; BELOSCAR, JUAN; THEUMER, MARTÍN GUSTAVO; QUINTANA, FRANCISCO JAVIER; PEREZ, ANA ROSA; MOTRÁN, CLAUDIA CRISTINA

Frontiers in Immunology

Frontiers Media SA

Año: 2024 vol. 14 p. 1 - 1

ntroduction: Chagas disease causes a cardiac illness characterized by immunoinflammatory reactions leading to myocardial fibrosis and remodeling. The development of Chronic Chagas Cardiomyopathy (CCC) in some patients while others remain asymptomatic is not fully understood, but dysregulated inflammatory responses are implicated. The Aryl hydrocarbon receptor (AhR) plays a crucial role in regulating inflammation. Certain tryptophan (Trp) metabolites have been identified as AhR ligands with regulatory functions. Methods, results, and discussion: We investigated AhR expression, agonist response, ligand production, and AhR-dependent responses, such as IDO activation and regulatory T (Treg) cells induction, in two T. cruzi-infected mouse strains (B6 and Balb/c) showing different polymorphisms in AhR. Furthermore, we assessed the metabolic profile of Trp catabolites and AhR agonistic activity levels in plasma samples from patients with chronic Chagas disease (CCD) and healthy donors (HD) u