SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE (SLAM): A MOLECULE THAT COUNTERACTS M. TUBERCULOSIS MACROPHAGES? IMMUNE EVASION?

BARBERO AM; HERNÁNDEZ DEL PINO RE; CELANO J; ESTERMANN M; TROTTA A; GENOULA M; BALBOA L; BARRIONUEVO P; PASQUINELLI V

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología (SAI); 2018

Sociedad Argentina de Inmunología (SAI)

Far from being an eradicated disease, Tuberculosis is nowadays the leading cause of death from a pathogen worldwide. Mycobacterium tuberculosis (Mtb) has smartly manipulated the immune system to survive within macrophages over ages. The costimulatory molecule SLAM is a self-ligand receptor that can internalize Gram-negative bacteria and regulate macrophages' phagosomal functions. In tuberculosis SLAM promotes Th1 protective responses. Here we studied SLAM modulation during Mtb infection and its role on macrophages? functions. Human monocyte-derived macrophages were obtained from healthy donors by CD14 positive selection. After 2h of adherence, cells were cultured in complete media overnight before stimulation with sonicated Mtb. THP-1 cells differentiated with PMA and stimulated with Mtb were also used. In some experiments macrophages were additionally stimulated with rhIFN-γ, rhIL-4, rhIL-10 or agonistic anti-SLAM antibody. Our results showed that Mtb-induced SLAM expression, determined by flow cytometry, was increased by IFN-γ and IL-10 treatment. No changes where observed with IL-4. Moreover, IFN-γ increased TNF-α secretion in Mtb-stimulated THP-1 cells as measured by ELISA. Rhodamine-stained Mtb (Mtb-R) was used to study SLAM role on bacterial uptake by flow cytometry. Anti-SLAM treatment further induced Mtb-R phagocytosis (p