Mycobacterium tuberculosis latency antigens modulate monocytes function from infected individuals

CASTELLO FLORENCIA; NANCY L. TATEOSIÁN; AMIANO NICOLAS; RODRIGO HERNANDEZ DEL PINO; JOAQUIN PELLEGRINI; ROLANDELLI AGUSTIN; GUTIERREZ MARISA; DOMINGO PALMERO; GARCIA VE

Congreso; IV Congreso de la Sociedad Latinoamericana de Inmunodeficiencias (LASID), LXIII Reunión de la Sociedad Argentina de Inmunología (SAI) y II Reunión FAIC (French-Argentinean Immunology Congress).; 2015

Background: One third of the world population is latently infected (LTBI) with Mycobacterium tuberculosis (Mtb), and at high risk of re-activating tuberculosis disease. BCG vaccination is not able to stop tuberculosis epidemic. To establish new prevention strategies, it is crucial to understand the alterations on antigen presenting cells (APC) and how Mtb latency antigens manipulate APC functions. Therefore, we investigated the effect of Hspx and Rv2626 on APC´s maturation and function of cells from controls and infected individuals. Methods: Peripheral blood mononuclear cells (PBMCs) from healthy donors (HD), patients with active tuberculosis (TB), and LTBI subjects were cultivated for 5 days with sonicated-Mtb (Mtb-Ag), or Mtb latency antigens, HspX and Rv2626c (2.5 microg/ml). Then, Tim-3, PD-L1, MHC-I and CD14 expression was determined by Flow cytometry. PBMCs were cultivated for 16h without stimulus to allow monocyte adherence. Afterwards, cells were stimulated with the antigens for 5 days and IL-12p70 production was determined in cells supernatants by ELISA.Results: By determining Tim-3 on the three groups of individuals, we observed that Mtb-Ag, Hspx and Rv2626 markedly decreased its expression on CD14+ cells in HD and TB patients. In contrast, in LTBI subjects, HspX and Rv2626c significantly increased Tim-3+CD14+ cells. Besides, whereas Mtb-Ag significantly augmented PD-L1 levels on CD14+ cells from all groups of individuals, Rv2626c and HspX antigens increased PD-L1 expression in HD and LTBI, but not in TB. Interestingly, Mtb-Ag, Rv2626c and HspX stimulation decreased MHC-I expression on LTBI CD14+cells. Finally, Rv2626c and HspX induced IL-12p70 production only from LTBI´s monocytes. Conclusions: Rv2626c and HspX latency antigens modulate the expression of inhibitory receptors and cytokine secretion on APC in Mtb infected individuals.