Role of SLAM on macrophages functions against Mycobacterium tuberculosis.

BARBERO AM; ALVAREZ GI; HERNÁNDEZ DEL PINO RE; PALACIO VG; GARCÍA VE; PASQUINELLI V

CAPITAL FEDERAL

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

LASID, SAI, FAIC.

Tuberculosis affects one-third of world´s population and millions of new cases are reported annually. Mycobacterium tuberculosis (Mtb) has the ability to survive within host´s macrophages which is key to its persistence and pathogenesis. Signaling lymphocyte-activation molecule (SLAM), expressed in hematopoietic cells, is a self-ligand and a costimulatory molecule that enhance Th1 response against Mtb. SLAM can also act as a bacterial sensor regulating Gram-negative bacteria removal from macrophages. Here, we explored SLAM role on macrophages functions against Mtb. Methods. THP-1 cells differentiated with PMA were stimulated with sonicated-Mtb. Human monocyte derived macrophages were obtain from healthy donors. SLAM expression was determined by flow cytometry (FC) and bacterial uptake by using rhodamine-stained Mtb. 6-carboxy-2´,7´-dichlorodihydrofluorescein diacetate was used to measure reactive oxygen species (ROS) by FC in macrophages stimulated with Mtb plus agonistic anti-SLAM . SLAM/CD107b (a late endosome marker) co-expression was evaluated by fluorescence microscopy.Results. Our findings show that Mtb induces SLAM expression in differentiated THP-1 cells unlike to macrophages which have strong constitutive levels. Interestingly, the great majority of phagocytic macrophages (84.82%) were SLAM+ as seen by rhodamine-Mtb uptake.The percentages of ROS+ cells were similar between macrophages stimulated with Mtb and those additionally costimulated through SLAM. However, SLAM costimulation enhanced the medium intensity fluorescence suggesting that SLAM induces ROS production. Moreover, preliminary results indicate that CD107b is co-expressed with SLAM in THP-1 cells.Conclusions. Our results show that macrophages´s SLAM expression enhance the microbicidal response against Mtb. Further studies are needed to show SLAM role as a mycobacterial sensor.