IFN-gamma production during active tuberculosis is regulated by mechanisms that involve IL-17, SLAM, and CREB.

VIRGINIA PASQUINELLI; JAMES C. TOWNSEND; JAVIER O. JURADO; IVANA B. ALVAREZ; MARÍA F. QUIROGA; PETER F. BARNES; BUKA SAMTEN; VERÓNICA E. GARCÍA

JOURNAL OF INFECTIOUS DISEASES

UNIV CHICAGO PRESS

Año: 2009 vol. 19 p. 661 - 665

0022-1899

Interferon-gamma (IFN-gamma) is crucial for protection against Mycobacterium tuberculosis, and the transcription factor cAMP response element binding protein (CREB) increases IFN-gamma transcription. We determined whether the transmembrane receptor signaling lymphocyte activation molecule (SLAM) and interleukin-17 (IL-17) affect CREB phosphorylation and IFN-gamma production in persons with tuberculosis. When T cells from patients with tuberculosis were activated with M. tuberculosis, 80% of SLAM(+) T cells expressed phosphorylated CREB, and SLAM activation increased CREB phosphorylation and IFN-gamma production. In contrast, IL-17 down-regulated SLAM expression, CREB phosphorylation, and IFN-gamma production. Therefore, IL-17 and SLAM have opposing effects on IFN-gamma production through CREB activation in persons with tuberculosis.