Special Section: Tuberculosis

Tuberculosis retains its foothold among human populations despite increasing implementation of highly effective control measures around the world. Highburden countries would benefit from interventions that decrease disease transmission. As the majority of new cases of tuberculosis arise from patients with cavitary pulmonary disease, strategies targeting this group of patients could significantly impact disease transmission, as well as improve cure rates and decrease antimicrobial resistance. Pulmonary cavities develop late in the course of tuberculous disease, and a preponderance of the evidence suggests that the host immune response is instrumental in producing these lesions. Data from mice, rabbits and humans suggest a role for tissue-damaging enzymes released from macrophages and neutrophils and the inflammatory effects of tumour necrosis factor, interferon-γ, interleukin-4 (IL-4), and IL-12 in cavity formation. Less well studied has been the pathogen’s contribution to this process, although various mycobacterial factors, including lipoarabinomannan, ESAT-6, and cord factor, are known to directly cause or exacerbate tissue damage. A major obstacle to the study of this characteristic human lesion – the lack of a rapid and reproducible animal model – has been overcome by a recently-developed bronchoscopic rabbit model of cavitary pulmonary tuberculosis. Exploring this model with current immunology and molecular techniques is expected to yield new insights into the pathogenesis and prevention of this destructive process.