Mycobacterium tuberculosis latency antigens modulate monocytes function from infected individuals

CASTELLO FLORENCIA A; TATEOSIAN NANCY L; AMIANO NICOLAS O; HERNANDEZ DEL PINO RODRIGO; PELLEGRINI JOAQUIN M; ROLANDELLI AGUSTIN; GUTIERREZ MARISA; PALMERO DOMINGO J; GARCÍA VERÓNICA E

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 islatently infected (LTBI) with Mycobacterium tuberculosis (Mtb),and at high risk of re-activating tuberculosis disease. BCGvaccination is not able to stop tuberculosis epidemic. To establishnew prevention strategies, it is crucial to understand the alterationson antigen presenting cells(APC) and how Mtb latency antigensmanipulate APC functions. Therefore, we investigated the effectof Hspx and Rv2626 on APC´s maturation and function of cellsfrom controls and infected individuals.Methods: Peripheral blood mononuclear cells(PBMCs) fromhealthy donors(HD), patients with active tuberculosis(TB), andLTBI subjects were cultivated (5 days) with sonicated-Mtb (MtbAg),or Mtb latency antigens, HspX and Rv2626c(2.5microg/ml).Then, Tim-3, PD-L1, MHC-I and CD14 expression wasdetermined by Flow cytometry. Monocytes were stimulated withthe antigens (5 days) and IL-12p70 production was determined insupernatants by ELISA.Results: By determining Tim-3 on the three groups of individuals,we observed that Mtb-Ag, Hspx and Rv2626 markedly decreasedits 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 significantlyaugmented PD-L1 levels on CD14+ cells from all groups ofindividuals, Rv2626c and HspX antigens increased PD-L1expression in HD and LTBI, but not in TB. Interestingly, Mtb-Ag,Rv2626c and HspX stimulation decreased MHC-I expression onLTBI CD14+cells. Finally, Rv2626c and HspX induced IL-12p70production only from LTBI´s monocytes. Conclusions: Rv2626cand HspX latency antigens modulate the expression of inhibitoryreceptors and cytokine secretion on APC in Mtb infectedindividuals.