p38 and Erk kinases regulate IFN-g production during human tuberculosis

PASQUINELLI V; ROVETTA AI; ALVAREZ IB; JURADO JO; GARCIA VE

Vancouver

Simposio; Keystone Symposia Conference. Tuberculosis: Immunology, Cell Biology and Novel Vaccination Strategies.; 2011

The importance of IFN-g in the protection against M. tuberculosis (Mtb) has been widely recognized. Previously, we reported that signaling lymphocytic activation molecule (SLAM) promotes Th1 responses during mycobacterial infections. We also demonstrated that the induction of IFN-g mediated by SLAM depends, at least in part, on CREB activation. To further analyze the signaling pathways induced by SLAM that contribute to CREB activation and IFN-g secretion in tuberculosis, we studied the role of two protein kinases: Erk and p38. Our results showed that M. tuberculosis induced the expression of Erk and p38MAPK. Moreover, inhibition of Erk or p38 pathway down-regulated both SLAM and IFN-g expression. Interestingly, p38MAPK regulated IFN-g production by a mechanism involving CREB, whereas Erk regulation of IFN-g would be CREB independent. Together, these data contribute with new information about the molecular basis operating during SLAM ligation that leads to IFN-g production in human tuberculosis.