Immunological control of tuberculosis: role of tumour necrosis factor and more.

Therapy of autoimmune diseases with tumour necrosis factor (TNF) neutralising agents has provided a unique opportunity to learn about the significance of TNF in the maintenance of latent bacterial infections in humans. The remarkably high incidence of tuberculosis in patients treated with TNF antagonists raises the intriguing question about the physiological role of TNF in maintaining the lifelong latency of tubercle bacilli in granulomas in infected patients. Basic research during the past decade(s) combined with thoughtful observations in human subjects with tuberculosis and autoimmune diseases has provided several potential explanations for the recurrence of tuberculosis if TNF supply is withdrawn. TNF is involved in at least four key functions that contribute towards beneficial effects on the symptoms of autoimmune disorders on the one hand, and the attenuation of immune responses against Mycobacterium tuberculosis on the other hand. These are outlined in this review: induction of apoptosis, maturation of dendritic cells, activation of antimicrobial activity in macrophages, and orchestration of leucocyte movement.