SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE (SLAM) AS A REGULATOR OF MACROPHAGES FUNCTIONS

BARBERO AM; CELANO J; ESTERMANN MA; HERNÁNDEZ DEL PINO RE; BALBOA L; BARRIONUEVO P; GARCÍA VE; PASQUINELLI V

Mar del Plata

Congreso; Reunión Anual de la Sociedad Argentina de Inmunología; 2016

Sociedad Argentina de Inmunología

Tuberculosis ranks alongside HIV as a leading cause of death worldwide affecting one third of world?s population. Mycobacterium tuberculosis (Mtb) has developed many strategies to evade immune response and survive within host?s macrophages (Mφ). SLAM is a receptor restricted to hematopoietic cells, a self-ligand and a costimulatory molecule that promotes protective Th1 response against Mtb. SLAM can also act as a microbial sensor that regulates Gram- bacterial phagosome functions in Mφ. Here, we study the role of SLAM in the immune response against Mtb on human Mφ activation and functions.We found that Mtb induces SLAM expression in human primary Mφ and THP-1 cells. SLAM is expressed on CD14+ cells from pleural effusions of patients with active TB suggesting that this molecule could have a role during active disease. The great majority of phagocytic Mφ were SLAM+, suggesting a role of SLAM during phagocytosis. IFN-γ stimulation significantly increased SLAM expression on Mtb stimulated Mφ and the number of SLAM+ rhodamine+ cells. SLAM downregulates VEGF production induced by Mtb on THP1 cells. VEGF has been associated with M2 phenotype and it has been shown that interception of host angiogenic signaling limits mycobacterial growth. Therefore VEGFa regulation by SLAM could have a dual role inducing a M1 phenotype and limiting mycobacterial growth through regulation of angiogenesis.The treatment of human macrophages with the acellular fraction of tuberculous pleural effusions downregulates SLAM expression, which could be associated with immunosuppressive properties on the pleural fluids that could lead to permissiveness for Mtb intracellular growth through downregulation of SLAM among other several mechanisms. Finally, SLAM co-localizes with the endosome marker EEA1 in Mtb stimulated cells, suggesting that SLAM could be a microbial sensor of Mtb as has been suggested for gram negative bacteria. Taken together, these results demonstrate that SLAM could be a key player of Mφ functions during Mtb infection.