Elkington PT, D’Armiento JM, Friedland JS. Tuberculosis immunopathology: the neglected role of extracellular matrix destruction. Sci Transl Med. 2011 Feb 23;3(71):71ps6.

In today’s article, Elkington, et al., would like to change how researchers view and define immunopathology in tuberculosis. The immune response to tuberculosis (TB) and resulting tissue damage has been recognized as a cause of mortality in TB patients but the terms such “caseous necrosis” used to capture what occurs during disease maybe inadequate.

In the past, the role of proteases and other enzymes in the breakdown of lung tissue and the formation of cavities was recognized by pioneers such as Lure and Dannenberg. Recent models of cavity formation have seem to ignore this role and focused more on immune cell and cytokine responses. Caseous necrosis is viewed as one process.

The authors suggest that the term “caseous necrosis” should actually be split into three processes: 1) The toxicity of Mycobacterium tuberculosis infection on macrophages causes cell necrosis 2) The response by activated T cells is a driver of the pathology 3) Protease activity works to break down the extracellular matrix of the lung.

This changed model identifies a target for antituberculous drugs with already identified compounds such as Doxycycline which is currently used for periodontal disease and a potent collangenase inhibitor, Ro32-3555 which has completed Phase III testing for arthritis. Targeting the enzymes responsible for the destruction of the extracellular matrix of the lung may help reduce the morbidity and mortality caused by TB.

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