Monocytes from chagasic patients are hyperinflammatory: Characterization of hypoxia response pathways in different monocyte subsets

VISCONTI, LM; RAMELLO, MC; AOKI, MP; SANMARCO, LM; EBERHARDT, N; MINGUEZ, RA; PONCE, NE; ELIZONDO, D

Simposio; Keystone Symposia meeting on Mononuclear Phagocytes in Health, Immune Defense and Disease; 2017

Monocytes (MO)represent a heterogeneous population of innate immune effector cells. Threedifferent subsets can be distinguished in humans: classical (CD14++CD16-), intermediate(CD14++CD16+), and non-classical MO (CD14+CD16++). Considering that different humaninflammatory diseases evidence MO subset perturbations, our aim was to characterizethe effect of chronic Chagas disease on the frequency and properties ofdifferent circulating MO subpopulations. We observed that seropositiveindividuals showed a higher frequency of hypoxia inducible factor (HIF)-1α+ MOcompared to seronegative donors (p<0.05). In accordance, chagasic patientsshowed increased frequency of IL-1β and nitric oxide (NO)-producing MO(p<0.05). Furthermore, MO from seropositive patients seemed to have greaterability to hydrolyze ATP, since they exhibited higher CD39 and CD73 expression thanMO from seronegative donors. The in vitroinfection of peripheral blood cells from healthy donors with Trypanosoma cruzi significantly diminishedCD73 expression in MO (p<0.05). Similar to bacterial and viral infections,the proportion of classical MO decreased (p<0.0001), while the frequency ofnon-classical subset increased (p<0.01) in chagasic patients. Non-classical MOpresented increased NO and ROS production and less IL-10 production thanclassical MO. Although in control donors the frequency of HIF-1α+classical MO was higher in comparison with non-classical MO; in seropositivepatients the percentage of HIF-1α+ non-classical MO was higher than HIF-1α+ classicalMO. Our data suggest that MO from chagasic patients exhibited augmented expressionof HIF-1α-target genes, suggesting that they may play important roles in maintaininginflammation during chronic human diseases.