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

SANMARCO, LILIANA MARÍA; EBERHARDT, NATALIA; BERGERO, GASTÓN; QUEBRADA PALACIO, LUZ PIEDAD; MARTINO ADAMI, PAMELA; 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

hagas disease is a life-long 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 higher frequency of hypoxia inducible factor (HIF)-1α and increased expression of its target genes/proteins. Non-classical monocytes are expanded in patients´ peripheral blood and represent an important source of NO. Monocytes entail CD8 T cell surface nitration since both the frequency of non-classical 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/macro