IFN-gamma production during active tuberculosis is regulated by mechanisms that involve IL-17, SLAM, and CREB.
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.
Pasquinelli
Virginia
V
Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Buenos Aires, Argentina.
Townsend
James C
JC
Jurado
Javier O
JO
Alvarez
Ivana B
IB
Quiroga
María F
MF
Barnes
Peter F
PF
Samten
Buka
B
García
Verónica E
VE
D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism*; D015964:Gene Expression Regulation, Bacterial / Q000502:physiology; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism*; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D014376:Tuberculosis / Q000276:immunology* / Q000378:metabolism
D015703:Antigens, CD; C115163:CREB1 protein, human; D017362:Cyclic AMP Response Element-Binding Protein; D020381:Interleukin-17; D011956:Receptors, Cell Surface; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D007371:Interferon-gamma