Reduced Trp-IDO-AhR Axis Activity is Associated with Higher Levels of Inflammatory Cytokines in Patients with Severe Chronic Chagas Cardiomyopathy

AMBROSIO, LAURA F.; VOLPINI, XIMENA; BRAJIN, AGUSTINA; THEUMER, MARTIN GUSTAVO; FOZZATTI, LAURA; BELOSCAR, JUAN; CERVI, LAP; QUINTANA, FRANCISCO; PEREZ, ANA ROSA; MOTRAN, CLAUDIA C

Mar del Plata

Congreso; REUNION ANULA SAI-SAIC-SAFE; 2018

SAIC-SAI

After acute infection with T. cruzi approximately 30% of infected individuals develop Chronic Chagas cardiomyopathy (CCC) while the rest remain asymptomatic (Asy). Although the mechanisms underlying the differential progression to CCC are still not fully understood, CCC display a more intense inflammatory response than Asy patients, who appear to have a more regulated immune response. We have reported that the indoleamine 2,3 dioxygenase-tryptophan metabolites-aryl hydrocarbon receptor (IDO-Trp-AhR) axis is associated with both the development of a strong Th1 response able to control parasite replication and its regulation by inducing, depending on the levels of AhR activation, Treg or IL-10+ producing cells. AhR can be activated by several ligands many of them being derivatives of Trp, such as L-kynurenine (Kyn) generated by IDO activity. To determine whether IDO-Trp-AhR axis is associated with CCC development, we analyzed the levels of IL-6, TNF, Trp metabolites and AhR agonists in serum samples from healthy controls, CCC and Asy patients by using ELISA, HPLC, targeted LC-MS and AhR agonistic activity. CCC patients were subclassified as Mild (altered ECG without congestive cardiac failure) or Severe (altered ECG, congestive cardiac failure and other alterations). By using a luciferase plasmid reporter assay we detected a decreased global AhR agonistic activity in infected patient sera as compared to healthy controls (p