IL-6 improves the nitric oxide-induced cytotoxic CD8+ T cell dysfunction in human chagas disease

SANMARCO, LILIANA MARIA; VISCONTI, LAURA MARINA; EBERHARDT, NATALIA; RAMELLO, MARIA CECILIA; PONCE, NICOLÁS ERIC; SPITALE, NATALIA BEATRIZ; VOZZA, MARIA LOLA; BERNARDI, GERMÁN ANDRÉS; GEA, SUSANA; MINGUEZ, ANGEL RAMÓN; AOKI, MARIA PILAR

Frontiers in Immunology

Frontiers Research Foundation

Año: 2016 vol. 7

eactive oxygen and nitrogen species are important microbicidal agents and are also involved in lymphocyte unresponsiveness during experimental infections. Many of the biological effects attributed to nitric oxide are mediated by peroxynitrites, which induce the nitration of immune cells, among others. Our group has demonstrated that nitric oxide is involved in the suppressive activity of myeloid-derived suppressor cells in Trypanosoma cruzi-infected mice, with a higher number of CD8+ T cells suffering surface-nitration compared to uninfected controls. Studying the functional and phenotypic features of peripheral CD8+ T cells from chagasic patients and human cells experimentally infected with T. cruzi, we found that different regulatory mechanisms impaired the effector functions of T cytotoxic population from seropositive patients. Peripheral leukocytes from chagasic patients showed increased nitric oxide production concomitant with increased tyrosine nitration of CD8+ T cells. Additio