Screening of phosphorylated immunoreceptors in patients with active tuberculosis: regulatory role of NTB-A

PELLEGRINI, J.M.; ROVETTA, A.I.; HERNANDEZ DEL PINO, R.E.; SOMOZA, M. ; AMIANO, N.O.; ROLANDELLI, A.; GUTIERREZ, M.; PALMERO, D.J.; GARCÍA, V.

Mar del Plata

Congreso; LXII Reunión Anual de la Sociedad Argentina de Inmunología; 2014

Sociedad Argentina de Inmunología

Tuberculosis (TB), a disease produced by Mycobacterium tuberculosis (Mtb), causes nearly 2 million deaths annually1. A Th1 response is required to achieve a protective immune response against Mtb, since the production of IFN-γ by T cells is critical for disease control2,3,4. In fact, the levels of Mtb-induced IFN-γ secreted by cells from TB patients are markedly lower than those produced by lymphocytes from healthy donors (HD). Cytokine production by T cells can be influenced through the activation/blockage of costimulatory molecules, cytokines themselves or immunomodulatory molecules, among others. Previously, we reported that the expression of the receptors SLAM and ICOS was increased in Th1 cells after Mtb lysate (Mtb-Ag) stimulation5,6. Furthermore, signaling through SLAM or ICOS augmented IFN-g secretion during active TB. Moreover, the SLAM-associated protein (SAP), CD31 and PD-1 interfered with Th1 responses in TB5,7,8. In view of these results, in this study we used a screening array of phosphorylated immunoreceptors to identify molecules with differential phosphorylation in peripheral blood mononuclear cells (PBMC) from TB patients and HD upon stimulation with Mtb-Ag. Our results showed marked differences in several receptors (ILT2/CD85j, ILT4/CD85d, CD31). Particularly, we found a marked decrease in the phosphorylation of NTB-A (a SLAM family receptor member). Next, we analyzed the levels of NTB-A by flow cytometry. Surprisingly, 90% of T cells from TB patients and HD expressed the receptor, which was not modulated by Mtb-Ag. Nevertheless, the blockage of NTB-A in Mtb-Ag-stimulated cells, significantly diminished the production of IFN-γ and IL-17 in both groups of individuals (p