Understanding the tuberculosis granuloma: the matrix revolutions

Abstract

Mycobacterium tuberculosis ( Mtb) causes the human disease tuberculosis (TB) and remains the top global infectious pandemic after coronavirus disease 2019 (COVID-19). Furthermore, TB has killed many more humans than any other pathogen, after prolonged coevolution to optimise its pathogenic strategies. Full understanding of fundamental disease processes in humans is necessary to successfully combat this highly successful pathogen. While the importance of immunodeficiency has been long recognised, biologic therapies and unbiased approaches are providing unprecedented insights into the intricacy of the host–pathogen interaction. The nature of a protective response is more complex than previously hypothesised. Here, we integrate recent evidence from human studies and unbiased approaches to consider how Mtb causes human TB and highlight the recurring theme of extracellular matrix (ECM) turnover.

An Improved Diagnostic of the Mycobacterium tuberculosis Drug Resistance Status by Applying a Decision Tree to Probabilities Assigned by the CatBoost Multiclassifier of Matrix Metalloproteinases Biomarkers

“…Finally, it is worth noting that the level of matrix metalloproteinases not only serves as a biomarker of the drug resistance of the Mycobacterium tuberculosis causing the illness but is directly related to its development and outcome. This induced a number of machine learning-based studies focused specifically on tissue destruction and treatment prognosis (see, e.g., [ 33 , 34 ]).…”

Immunosuppressive Mechanisms in Brucellosis in Light of Chronic Bacterial Diseases

“…Overall, a better understanding of the key players during persistent infections, such as type I and III IFNs, or adipose tissues as reservoirs and sources of immune modulators, is an imperative for a proper delivery of targeted drugs to clear these intracellular bacterial pathogens. Another HDT approach suggested in the context of TB infection is the disruption of the granuloma, as an opportunity to improve the ability of crucial immune cell types to reach the bacterial niche, recognise, and eliminate bacteria [373,374]. This type of scheme might also enhance the penetration of drugs at the right place, since many of them have demonstrated effectiveness in vitro but failed to translate into new clinical antibiotics [373].…”

“…Another HDT approach suggested in the context of TB infection is the disruption of the granuloma, as an opportunity to improve the ability of crucial immune cell types to reach the bacterial niche, recognise, and eliminate bacteria [ 373 , 374 ]. This type of scheme might also enhance the penetration of drugs at the right place, since many of them have demonstrated effectiveness in vitro but failed to translate into new clinical antibiotics [ 373 ].…”

Proteomics in Biomarker Discovery for Tuberculosis: Current Status and Future Perspectives

“…Mtb is an intracellular pathogen that preferentially infects host macrophages and primarily resides within lung granulomas ( Brites and Gagneux, 2015 ; Elkington et al, 2021 ), making directly detecting Mtb in human body fluids, such as blood, saliva, or urine, impossible. A current challenge in TB diagnosis is the development of rapid point-of-care tests.…”