Tumor Necrosis Factor and Chemokine Interactions in the Formation and Maintenance of Granulomas in Tuberculosis

Abstract

Inflammatory cells migrate to the lungs in response to Mycobacterium tuberculosis infection. These infiltrating cells organize into a structure called a granuloma, which controls and contains infection. The signals that influence the formation of granulomas are largely unknown. Tumor necrosis factor (TNF) has been demonstrated to be required for formation of granulomas, in mouse models of tuberculosis, and for control of latent tuberculosis, in humans. We investigated the mechanisms by which TNF controls cell migration in response to M. tuberculosis infection, focusing on the effects of this cytokine on chemokine expression. Chemokines are small molecules that direct the migration of cells within the body. Our data support the notion that TNF is required for appropriate chemokine expression by M. tuberculosis-infected macrophages, both in vitro and in vivo.