Tumor necrosis factor and tuberculosis

Tumor necrosis factor (TNF) plays a major role in the initial and long-term control of tuberculosis. The mechanisms by which this cytokine contributes to the control of Mycobacterium tuberculosis infection are numerous and therefore difficult to dissect. TNF is important in macrophage activation as well as cell recruitment to the site of infection. It is the primary signal important in granuloma formation, as neutralization of this cytokine leads to lack of control of initial or chronic infection, and loss of granuloma structure. In humans treated with TNF-neutralizing drugs, an increased susceptibility to tuberculosis, as well as other infectious diseases, is observed. We are using animal models to understand how TNF neutralization by these drugs can lead to reactivation of tuberculosis.