Signaling through SLAM involves p38MAPK activation in patients with active tuberculosis.

VIRGINIA PASQUINELLI; ANA I. ROVETTA; RODRIGO HERNANDEZ DEL PINO; IVANA B ALVAREZ; JAVIER O JURADO; ROMINA ASPERA; NELLY ZAMBRANA; ROSA M. MUSELLA; VERÓNICA E. GARCÍA

Buenos Aires

Congreso; 1er Congreso Franco-Argentino de Inmunología; 2010

The importance of IFN-γ for the protection against M. tuberculosis (Mtb) has been widely recognized. Previously we reported that signaling lymphocytic activation molecule (SLAM) activation promotes Th1 responses during mycobacterial infections. We also demonstrated that the induction of IFN-γ mediated by SLAM in tuberculosis depends, at least in part, on CREB activation. Moreover, we showed that SLAM signaling induced the activation of the protein kinase Erk. To further analyze the signaling pathways induced by SLAM that contribute to CREB activation and IFN-γ secretion in tuberculosis, we studied the role of p38MAPK. Our results showed that the addition of the p38MAPK inhibitor SB22026 to Mtb stimulated cells from tuberculosis patients and healthy donors inhibited the percentage of IFN-γ+pCREB+ T cells by more than 70%, indicating that p38 would be involved in the activation of CREB. Since, the p38 inhibitor downregulates the expression of SLAM induced by Mtb, we stimulated peripheral blood mononuclear cells from tuberculosis patients and healthy donors for 5 days with the antigen. Cells were then washed and stimulated with SB22026 plus an agonistic α-SLAM mAb. After 48h the production of IFN-γ was significantly decreased by the p38 inhibitor compared with the cells stimulated with Mtb + α-SLAM (p< 0.05). Taken together, these results indicate that the production of IFN-γ induced by SLAM signaling is mediated by Erk, p38 and CREB phosphorylation. Then, our data contribute with new information about the molecular basis operating during SLAM ligation that leads to IFN-γ production in human tuberculosis.