MODULATION OF AUTOPHAGY BY CYTOKINES DURING HUMAN ACTIVE TUBERCULOSIS

JOAQUÍN M. PELLEGRINI; NANCY L. TATEOSIAN; NICOLÁS O. AMIANO; AGUSTÍN ROLANDELLI; RODRIGO HERNÁNDEZ DEL PINO; ESTEFANÍA URDAÑIZ; LILIANA RONDON; MARIANA PIURI; NICOLÁS CASCO; MARISA GUTIERREZ; DOMINGO J. PALMERO; VERÓNICA E. GARCÍA

Capital Federal

Congreso; I Meeting LASID FAIC SAI; 2015

Abstract: BACKGROUND: Th1 responses are crucial in the host defense against Mycobacterium tuberculosis (Mtb) infection, but IFN-gamma alone is not sufficient to the complete bacterial eradication. Actually, Th17 cells have been associated with Mtb infection. Given that cytokines may modulate positively and negatively the autophagic response affecting mycobacterial survival, we investigated the role of IFN-gamma and IL-17A on autophagy during human active tuberculosis. METHODS: Peripheral blood mononuclear cells (PBMCs) from healthy donors (HD) and patients with active tuberculosis (TB) were cultivated for 16 h without stimulus to allow monocyte adherence. Cells were then either infected with a RD1 deleted-Mtb-strain (MtbDeltaRD1) or MtbH37Rv pathogenic strain, or stimulated with sonicated Mtb (Mtb-Ag) ± IFN-gamma (1.8ng/ml) or IL -17A (10ng/ml) for 24 h. Afterwards, autophagy levels were analyzed by Flow cytometry and Immunofluorescence Microscopy against LC3-IIB and IFN-gamma production was measured by ELISA. RESULTS: Mtb-Ag stimulation increased the levels of LC3?IIB in monocytes of TB patients. Importantly, when these stimulated cells were treated with IFN-gamma or IL-17A for 24 h, the induced levels of autophagy were significantly higher (p