Inflammation and Immunopathogenesis of Tuberculosis Progression

A lot of efforts have been made to elucidate immune mechanisms of TB defense. The studies have identified immune cells, molecules and pathways essential for TB protection. It has been demonstrated that protection depends primarily on the activity of Th1 lymphocytes and macrophages (Schluger & Rom, 1998; Flynn & Chan, 2001; Boom et al., 2003; North & Jung, 2004; Kaufmann, 2006). Th1 cells produce immune mediators, such as IFN- and TNF that activate macrophages. Activated macrophages produce bactericidal molecules (e.g., reactive nitrogen and oxygen species) that kill mycobacteria. Both macrophages and T cells secrete a wide range of soluble factors that promote migration of other immune cells to the site of infection. At the site, immune cells settle to form granuloma that prevents mycobacteria dissemination. Overall, immune protection depends on efficient pathogen killing (i.e., antibacterial response) and efficient concentration of immune cells at the site of infection (i.e., inflammatory response). Multiple studies have demonstrated that deficiency in cells and molecules implicated in either of these responses results in extremely severe TB, supporting a concept that TB develops as a result of immune deficiency. On the other hand, since Koch’s studies, TB has been considered as an immunopathological disease. In this concept, disease develops due to uncontrolled inflammatory reactivity of the host to the pathogen. Direct evidences for this concept had not been available, but are now accumulating, raising a general question on the role for immune deficiency and hyperreactivity in the pathogenesis of tuberculosis.