Tuberculosis Immunopathology: The Neglected Role of Extracellular Matrix Destruction

The extracellular matrix in the lung must be destroyed for Mycobacterium tuberculosis--the agent that causes tuberculosis (TB)--to spread. The current paradigm proposes that this destruction occurs as a result of the action of proinflammatory cytokines, chemokines, immune cells, and lipids that mediate TB-associated necrosis in the lung. However, this view neglects the fact that lung matrix can only be degraded by proteases. We propose an original conceptual framework of TB immunopathology that may lead directly to treatments that involve inhibition of matrix metalloproteinase activity to hinder matrix destruction and reduce the morbidity and mortality associated with TB.