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

Abstract

Interferon-γ (IFN-γ) is crucial for protection against Mycobacterium tuberculosis, and the transcription factor cAMP response element binding protein (CREB) increases IFN-γ transcription. We determined whether the transmembrane receptor signaling lymphocyte activation molecule (SLAM) and interleukin-17 (IL-17) affect CREB phosphorylation and IFN-γ 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-γ production. In contrast, IL-17 down-regulated SLAM expression, CREB phosphorylation, and IFN-γ production. Therefore, IL-17 and SLAM have opposing effects on IFN-γ production through CREB activation in persons with tuberculosis. © 2009 by the Infectious Diseases Society of America. All rights reserved.