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Collagen degradation in tuberculosis pathogenesis: the biochemical consequences of hosting an undesired guest (27 visite)
Biochem J (ISSN: 1470-8728electronic, 0264-6021linking, 0264-6021print), 2018 Oct 11; 475(19): 3123-3140.
Tipo di articolo: Journal Article, Review,
Impact factor: 4.897
Impact factor a 5 anni: 4.693
Parole chiave: Collagen, Protease, Structure, Tuberculosis,
Url: Non disponibile.
The scenario of chemical reactions prompted by the infection by Mycobacterium tuberculosis is huge. The infection generates a localized inflammatory response, with the recruitment of neutrophils, monocytes, and T-lymphocytes. Consequences of this immune reaction can be the eradication or containment of the infection, but these events can be deleterious to the host inasmuch as lung tissue can be destroyed. Indeed, a hallmark of tuberculosis (TB) is the formation of lung cavities, which increase disease development and transmission, as they are sites of high mycobacterial burden. Pulmonary cavitation is associated with antibiotic failure and the emergence of antibiotic resistance. For cavities to form, M. tuberculosis induces the overexpression of host proteases, like matrix metalloproteinases and cathepsin, which are secreted from monocyte-derived cells, neutrophils, and stromal cells. These proteases destroy the lung parenchyma, in particular the collagen constituent of the extracellular matrix (ECM). Namely, in an attempt to destroy infected cells, the immune reactions prompted by mycobacterial infections induce the destruction of vital regions of the lung, in a process that can become fatal. Here, we review structure and function of the main molecular actors of ECM degradation due to M. tuberculosis infection and the proposed mechanisms of tissue destruction, mainly attacking fibrillar collagen. Importantly, enzymes responsible for collagen destruction are emerging as key targets for adjunctive therapies to limit immunopathology in TB.
*** IBB - CNR ***
Institute of Biostructures and Bioimaging, CNR, Via Mezzocannone 16, I-80134 Napoli, Italy firstname.lastname@example.org.,
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