Signaling Lymphocytic Activation Molecule (SLAM): a molecule that counteracts M. tuberculosis macrophages? immune evasion?

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

Mar del Plata

Congreso; LXIII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXVI Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y Reunión de la Sociedad Argentina de Fisiología (SAFIS); 2018

SAIC, SAI y SAFIS

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-Υ and IL-10 treatment. No changes were observed with lL-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