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

BARBERO ANGELA MARIA; HERNANDEZ DEL PINO RODRIGO EMANUEL; CELANO JOSEFINA; ESTERMANN MARTIN; TROTTA ALDANA; GENOULA MELANIE; BALBOA LUCIANA; BARRIONUEVO PAULA; PASQUINELLI VIRGINIA

Mar del Plata

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

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-, 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- and IL-10 treatment. No changes where observed with lL-4. Moreover, IFN- increased TNF- 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