SLAM activation regulates cytokine microenvironment during active tuberculosis.

ROMINA ASPERA; IVANA BELÉN ÁLVAREZ; JAVIER O JURADO; DARÍO A FERNÁNDEZ DO PORTO; SANTIAGO ABAD; ROSA M. MUSELLA; VERONICA E GARCIA

Buenos Aires

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

Protective immunity against Mycobacterium tuberculosis (Mtb) requires the generation of cellular immune responses. In this context, IFNγ and TNFa production are crucial to fight this pathogen. Moreover, it has been recently suggested that IL-17 might also contribute to the resolution of tuberculosis. Previously we demonstrated that signaling through the signaling lymphocyte activation molecule (SLAM) increased IFNγ secretion in patients with tuberculosis. Furthermore, we reported that IL-17 decreased SLAM expression. Then, in this investigation we studied the role of SLAM activation on the regulation of the cytokine milieu in tuberculosis. Our results showed that after stimulation with Mtb antigen, most of CD4+ IL-17 secreting T cells expressed SLAM (IL-17+ SLAM+: 94.41%±3.38; IL-17+ SLAM-: 5.59±3.38%, p< 0.005, Wilcoxon Test). Moreover, signaling through SLAM significantly increased the production of IL-17 in tuberculosis patients (Mtb+ a-SLAM relative to Mtb: 246.9±78.23, p< 0.05, Wicoxon Test). In agreement with these data, blocking of SLAM by iRNA, significantly decreased IL-17 secretion. On the other hand, activation of SLAM induced a marked augment of TNFa production in patients with tuberculosis (Mtb: 23872 ± 8442pg/ml; Mtb + a-SLAM: 30715 ±10332 pg/ml, p< 0.05, Wilcoxon Test), but in contrast to IFNγ and IL-17, TNFa didn’t regulate SLAM expression on the surface of T cells. Taken together, our present results suggest that SLAM activation leads to the generation of a complex cytokine microenvironment during active tuberculosis, having a crucial role in the homeostasis of the host immune response against the bacteria.