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Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis


Neutrophil infiltration is characteristic of immune-induced pathology in tuberculosis but mechanisms whereby neutrophils cause tissue destruction are not fully understood. In this study, we show that neutrophils secrete the collagenase MMP-8 in response to direct infection with Mycobacterium tuberculosis and via cellular networks. MMP-8 is up-regulated in respiratory samples from TB patients, driving matrix destruction associated with neutrophil activation and reflects disease severity. Neutrophils are present adjacent to the wall of TB cavities in human histology specimens. The metabolic pathway AMP-activated protein kinase (AMPK) regulates neutrophil MMP-8 secretion with data supported by studies in human neutrophils from AMPK-deficient patients. Host-directed therapy against neutrophil MMP-8 may reduce innate-immune mediated tissue damage in TB.


Vyšlo v časopise: Neutrophil-Derived MMP-8 Drives AMPK-Dependent Matrix Destruction in Human Pulmonary Tuberculosis. PLoS Pathog 11(5): e32767. doi:10.1371/journal.ppat.1004917
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004917

Souhrn

Neutrophil infiltration is characteristic of immune-induced pathology in tuberculosis but mechanisms whereby neutrophils cause tissue destruction are not fully understood. In this study, we show that neutrophils secrete the collagenase MMP-8 in response to direct infection with Mycobacterium tuberculosis and via cellular networks. MMP-8 is up-regulated in respiratory samples from TB patients, driving matrix destruction associated with neutrophil activation and reflects disease severity. Neutrophils are present adjacent to the wall of TB cavities in human histology specimens. The metabolic pathway AMP-activated protein kinase (AMPK) regulates neutrophil MMP-8 secretion with data supported by studies in human neutrophils from AMPK-deficient patients. Host-directed therapy against neutrophil MMP-8 may reduce innate-immune mediated tissue damage in TB.


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Hygiena a epidemiológia Infekčné lekárstvo Laboratórium

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