Signaling Lymphocytic Ativation Molecule (SLAM) as a regulator of macrophages functions

BARBERO ANGELA MARIA; CELANO JOSEFINA; ESTERMANN MARTIN; HERNANDEZ DEL PINO RODRIGO EMANUEL; BALBOA LUCIANA; BARRIONUEVO PAUA; GARCIA VERONICA; PASQUINELLI VIRGINIA

Mar del Plata

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica (SAIC), LXIV Reunión Anual de la Sociedad Argentina de Inmunología (SAI) y LXVIII Reunión Anual de la Sociedad Argentina de Farmacología Experimental (SAFE).; 2016

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 selfligand and a costimulatory molecule that promotes Th1response against Mtb. SLAM can also act as microbial sensor that regulates Gram - bacterial phagosome functions in Mφ.Here, we study SLAM role against Mtb on Mφ activation and functions.Human monocyte derived Mφ were obtained from healthy donors after FicollPercollgradient. After adherence for 2h, the cells were culture in complete media for 1618h before stimulation with sonicated Mtb. SLAM, CD86 and CD163 expression was studied by flow cytometry and bacterial uptake by using rhodamine stained Mtb. In some experiments Mφ were also stimulated with IFNg or agonistic antibody αSLAM. Production of VEGF was measured by ELISA in THP1 cells differentiated with PMA and stimulated with Mtb.Our results show that Mtb induces SLAM expression in monocytes and Mφ. Interestingly, preliminary results indicate that these Mφ present high CD86 and low CD163 expression (M2 marker) suggesting that SLAM promotes M1 activation during Mtb infection. Moreover, the great majority of phagocytic Mφ (62.5%) were SLAM+ as seen by rhodamine Mtb uptake. However we found a reduction of phagocytosis when macrophages were treated with αSLAM. This could be due to a negative role of SLAM during phagocytosis or to a blocking effect of the interaction SLAMMtb. More studies are required to elucidate this function.IFNg stimulation significantly increased SLAM expression on MtbstimulatedMφ and the number of SLAM+ rhodamine+ cells.Moreover; a role of SLAM on angiogenesis was seen as the levels of VEGF were significantly decreased after αSLAM treatment on THP1 cells.Taken together, these results demonstrate the role of SLAM as a regulator of Mφ functions in response to Mtb infection.