P38 MAPK PATHWAY IS INVOLVED IN INERFERON GAMMA (IFN-gamma) PRODUCTION BY NATURAL KLLER CELLS (NK) FROM TUBERCULOUS PLEURISY

P. SCHIERLOH, N YOKOBORI, M ALEMÁN, R MUSELLA, M ROLDAN, E ABBATE, S DE LA BARRERA, SASIAIN MC.

Córdoba, Argentina.

Congreso; VII Congreso Latinoamericano de Inmunología.; 2005

Sociedad Latinoamericana de Inmunología.

The expression of interferon gamma (IFN-g) by CD3-CD56high cells from pleural effusions (PE-NK) of patients with tuberculosis (TB) is induced upon stimulation with Mycobacterium tuberculosis (Mtb). We determined the receptors and signaling pathways induced by Mtb on IFN-g production by employing pharmacological inhibitors of p38 MAPK, JUNK, ERK or PI3K pathways, and flow cytometry. IFN-g production by PE-NK cells was not dependent on CD3+ and CD14+ cells and was not mediated by NKG2D-MICA engagement. While IFN-g production was induced by the Mtb cell wall component manLAM (% NK IFN-g+: Mtb=55±10 vs Mtbmam LAM=20±8, p<0.05, n=5), the blockade of TLR2 inhibite 20% of IFN-g production. Only the inhibition of p38MAPK pathway abolished Mtb-induced IFN-g production (% NK IFN-g+: Mtb=47±6 vs Mtb+SB203580= 9±3, p<0.01). In accordance, the phosphorilation of p38MAPK was induced by Mtb in PE-NK cells (p<0,.05, n=4). Taking together these results demonstrate that IFN-g production by PE-NK cells is not dependent on the presence of CD14+ and CD3+ cells, suggesting a direct interaction of  CD56high cells and Mtb involving the p38MAPK pathway with receptors not yet identified.