Monocyte glycolysis determines CD8+ T cell functionality in human Chagas disease

SANMARCO, LILIANA MARÍA; EBERHARDT, NATALIA; BERGERO, GASTÓN; QUEBRADA PALACIO, LUZ PIEDAD; ADAMI, PAMELA MARTINO; VISCONTI, LAURA MARINA; MINGUEZ, ÁNGEL RAMÓN; HERNÁNDEZ-VASQUEZ, YOLANDA; CARRERA SILVA, EUGENIO ANTONIO; MORELLI, LAURA; POSTAN, MIRIAM; AOKI, MARIA PILAR

JCI Insight

American Society for Clinical Investigation

Año: 2019 vol. 4

hagas disease is a lifelong pathology resulting from Trypanosoma cruzi infection. It represents one of the most frequent causes of heart failure and sudden death in Latin America. Herein, we provide evidence that aerobic glycolytic pathway activation in monocytes drives nitric oxide (NO) production, triggering tyrosine nitration (TN) on CD8+ T cells and dysfunction in patients with chronic Chagas disease. Monocytes from patients exhibited a higher frequency of hypoxia-inducible factor 1α and increased expression of its target genes/proteins. Nonclassical monocytes are expanded in patients? peripheral blood and represent an important source of NO. Monocytes entail CD8+ T cell surface nitration because both the frequency of nonclassical monocytes and that of NO-producing monocytes positively correlated with the percentage of TN+ lymphocytes. Inhibition of glycolysis in in vitro?infected peripheral blood mononuclear cells decreased the inflammatory properties of monocytes/macrophage