Mycobacterium tuberculosis and the host response

Abstract

Mycobacterium tuberculosis remains a leading cause of morbidity and mortality worldwide. Advances reported at a recent international meeting highlight insights and controversies in the genetics of M. tuberculosis and the infected host, the nature of protective immune responses, adaptation of the bacillus to host-imposed stresses, animal models, and new techniques.

Figure 1.

A ribbon representation of the backbone topology of the CFP-10–ESAT-6 complex. Based on the closest converged structure fit to the mean, the model illustrates the two helix-turn-helix hairpin structures formed by the individual proteins. CFP-10, red; ESAT-6, blue. Image provided by Philip Renshaw (Leicester, UK).

Figure 2.

Schematic description of the underlying mechanism of improved T cell stimulation by a novel BCG vaccine. Recombinant BCG deleted in urease and expressing listeriolysin is capable of inducing a more profound immune response than wild-type BCG. The likely mechanism involves perforation of the phagosomal membrane, which allows leakage into the cytosol of both mycobacterial antigens and phagosomal enzymes such as cathepsins. Cathepsins are known to induce apoptosis. Thus, the new BCG vaccine strain induces crosspriming leading to a more efficacious immune response. Image provided by Stefan Kaufmann (Berlin, Germany) (25).

Figure 3.

Hypercholesterolemia predisposes to severe TB. ApoE-deficient mice fed on a high cholesterol diet develop giant lung inflammatory lesions when infected with M. tuberculosis. Image provided by Hardy Kornfield (Worcester, MA).

Figure 4.

Electron microscope images of the hexameric mycobacterial proteasome ATPase (Mpa). Compilation by Z. Chen and H. Li; images rotated about their axis (–5) to display the arbitrarily designated “top” (T) and “bottom” (B) of the complex. Reproduced from reference 13 by permission.