Mycobacterial antigens accumulation in foamy macrophages in murine pulmonary tuberculosis lesions: Association with necrosis and making of cavities

Riaz, Syeda Mariam; Bjune, Gunnar; Wiker, Harald G.; Sviland, Lisbeth; Mustafa, Tehmina

doi:10.1111/sji.12866

Cited by 12 publications

(12 citation statements)

References 25 publications

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“…Slowly progressive pulmonary TB in immunocompetent mice has additional correlates with the early lesion of PPTB [ 7 , 8 , 136 , 137 , 138 ]. It is an obstructive pneumonia with sparsely infected foamy alveolar macrophages that slowly accumulate host lipids and secreted mycobacterial antigens in a pattern similar to the human disease, Figure 8 .…”

Section: Animal Modelsmentioning

confidence: 99%

The Pathogenesis of Tuberculosis–The Koch Phenomenon Reinstated

Hunter

2020

Pathogens

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Research on the pathogenesis of tuberculosis (TB) has been hamstrung for half a century by the paradigm that granulomas are the hallmark of active disease. Human TB, in fact, produces two types of granulomas, neither of which is involved in the development of adult type or post-primary TB. This disease begins as the early lesion; a prolonged subclinical stockpiling of secreted mycobacterial antigens in foamy alveolar macrophages and nearby highly sensitized T cells in preparation for a massive necrotizing hypersensitivity reaction, the Koch Phenomenon, that produces caseous pneumonia that is either coughed out to form cavities or retained to become the focus of post-primary granulomas and fibrocaseous disease. Post-primary TB progresses if the antigens are continuously released and regresses when they are depleted. This revised paradigm is supported by nearly 200 years of research and suggests new approaches and animal models to investigate long standing mysteries of human TB and vaccines that inhibit the early lesion to finally end its transmission.

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Section: Animal Modelsmentioning

confidence: 99%

The Pathogenesis of Tuberculosis–The Koch Phenomenon Reinstated

Hunter

2020

Pathogens

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“…The main pathological features of TB include the transformation of foamy macrophages, the formation of granulomas, and the formation of pulmonary cavities with caseous necrosis. 2,3 The cell wall of M. tuberculosis is enriched in lipids such as lipoarabinomannan and trehalosedimycolate that can stimulate CD4+ T cells to secrete interferon-gamma (IFN-γ) 4 and may invoke the host immune response to form foam cells (macrophages). The whole-genome microarray analysis of M. tuberculosis revealed that lipopolysaccharides and lipid metabolism genes were highly expressed in caseous TB granulomas.…”

Section: Introductionmentioning

confidence: 99%

Identification of potential lipid biomarkers for active pulmonary tuberculosis using ultra-high-performance liquid chromatography-tandem mass spectrometry

Han

Chen

et al. 2020

Exp Biol Med (Maywood)

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Early diagnosis of active pulmonary tuberculosis (TB) is the key to controlling the disease. Host lipids are nutrient sources for the metabolism of Mycobacterium tuberculosis. In this research work, we used ultra-high-performance liquid chromatography-tandem mass spectrometry to screen plasma lipids in TB patients, lung cancer patients, community-acquired pneumonia patients, and normal healthy controls. Principal component analysis, orthogonal partial least squares discriminant analysis, and K-means clustering algorithm analysis were used to identify lipids with differential abundance. A total of 22 differential lipids were filtered out among all subjects. The plasma phospholipid levels were decreased, while the cholesterol ester levels were increased in patients with TB. We speculate that the infection of M. tuberculosis may regulate the lipid metabolism of TB patients and may promote host-assisted bacterial degradation of phospholipids and accumulation of cholesterol esters. This may be related to the formation of lung cavities with caseous necrosis. The results of receiver operating characteristic curve analysis revealed four lipids such as phosphatidylcholine (PC, 12:0/22:2), PC (16:0/18:2), cholesteryl ester (20:3), and sphingomyelin (d18:0/18:1) as potential biomarkers for early diagnosis of TB. The diagnostic model was fitted by using logistic regression analysis and combining the above four lipids with a sensitivity of 92.9%, a specificity of 82.4%, and the area under the curve (AUC) value of 0.934 (95% CI 0.873 – 0.971). The machine learning method (10-fold cross-validation) demonstrated that the model had good accuracy (0.908 AUC, 85.3% sensitivity, and 85.9% specificity). The lipids identified in this study may serve as novel biomarkers in TB diagnosis. Our research may pave the foundation for understanding the pathogenesis of TB.

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“…In our case, the patient presented with a single, noncaseating nodule. The skin biopsy showed large numbers of foamy macrophages, intense neoangiogenesis, and the perivascular cuffing of lymphocytes, which are described as initial signs of granuloma formation in murine models of primary pulmonary TB, 7 , 8 as also described by Russell et al 9 in the process of TB granuloma formation in humans. It is of note that in very early stage of such a lesion, Ziehl–Nielsen staining might be negative, contrary to what is reported for necrotic lesions.…”

Section: Discussionmentioning

confidence: 52%