A Spotlight on Liquefaction: Evidence from Clinical Settings and Experimental Models in Tuberculosis

Cardona, Père-Joan

doi:10.1155/2011/868246

Cited by 29 publications

(26 citation statements)

References 55 publications

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“…XPNPEP1 is a metalloaminopeptidase involved in the degradation of neuropeptides and the finding of VIP in these analyses is intriguing. Coagulation Factor V was the strongest differentially expressed marker at 8 weeks between responders and slow-responders and may suggest either better protein calorie nutrition in responders [38] or that tissue remodeling, changes in fibrinolysis and the resolution of pulmonary TB lesions has connections with the coagulation cascade that have not been described previously [39, 40]. …”

Section: Discussionmentioning

confidence: 99%

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis

et al. 2014

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Background New drug regimens of greater efficacy and shorter duration are needed for tuberculosis (TB) treatment. The identification of accurate, quantitative, non-culture based markers of treatment response would improve the efficiency of Phase 2 TB drug testing. Methods In an unbiased biomarker discovery approach, we applied a highly multiplexed, aptamer-based, proteomic technology to analyze serum samples collected at baseline and after 8 weeks of treatment from 39 patients with pulmonary TB from Kampala, Uganda enrolled in a Centers for Disease Control and Prevention (CDC) TB Trials Consortium Phase 2B treatment trial. Results We identified protein expression differences associated with 8-week culture status, including Coagulation Factor V, SAA, XPNPEP1, PSME1, IL-11 Rα, HSP70, Galectin-8, α2-Antiplasmin, ECM1, YES, IGFBP-1, CATZ, BGN, LYNB, and IL-7. Markers noted to have differential changes between responders and slow-responders included nectin-like protein 2, EphA1 (Ephrin type-A receptor 1), gp130, CNDP1, TGF-b RIII, MRC2, ADAM9, and CDON. A logistic regression model combining markers associated with 8-week culture status revealed an ROC curve with AUC=0.96, sensitivity=0.95 and specificity=0.90. Additional markers showed differential changes between responders and slow-responders (nectin-like protein), or correlated with time-to-culture-conversion (KLRK1). Conclusions Serum proteins involved in the coagulation cascade, neutrophil activity, immunity, inflammation, and tissue remodeling were found to be associated with TB treatment response. A quantitative, non-culture based, five-marker signature predictive of 8-week culture status was identified in this pilot study.

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Section: Discussionmentioning

confidence: 99%

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis

et al. 2014

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“…We may suppose that the evolution of a "double personality" would allow M. tuberculosis in its replicative form to escape from immunosurveillance to outgrow and colonize, but also to induce a strong immune response that contributes to tissue damage, shifting to dormancy. In fact, cavitation and damage of lung tissue and bronchi caused by immunopathology are necessary for M. tuberculosis to gain access to the environment and to be transmitted to susceptible individuals (10).…”

Section: Discussionmentioning

confidence: 99%

“…However, the host immune response may represent a double-edged sword in different TB stages: it has certainly a protective role, but it may also be detrimental to the host and instrumental to M. tuberculosis to infect other individuals (9). The immune response also contributes to causing tissue damage, caseum liquefaction (10), and eventually the formation of cavities merging into the bronchial tree. These open lesions permit the communication between TB foci and the external environment, thus making it possible for M. tuberculosis to diffuse in the environment by droplets.…”

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confidence: 99%

Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Mariotti

Pardini

Gagliardi

et al. 2013

The Journal of Immunology

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Dormancy is defined as a stable but reversible nonreplicating state of Mycobacterium tuberculosis. It is currently thought that dormant M. tuberculosis (D-Mtb) is responsible for latent tuberculosis (TB) infection. Recently, D-Mtb was also shown in sputa of patients with active TB, but the capacity of D-Mtb to stimulate specific immune responses was not investigated. We observed that purified protein derivative–specific human CD4+ T lymphocytes recognize mycobacterial Ags more efficiently when macrophages are infected with D-Mtb instead of replicating M. tuberculosis (R-Mtb). The different Ag recognition occurs even when the two forms of mycobacteria equally infect and stimulate macrophages, which secrete the same cytokine pattern and express MHC class I and II molecules at the same levels. However, D-Mtb but not R-Mtb colocalizes with mature phagolysosome marker LAMP-1 and with vacuolar proton ATPase in macrophages. D-Mtb, unlike R-Mtb, is unable to interfere with phagosome pH and does not inhibit the proteolytic efficiency of macrophages. We show that D-Mtb downmodulates the gene Rv3875 encoding for ESAT-6, which is required by R-Mtb to block phagosome maturation together with Rv3310 gene product SapM, previously shown to be downregulated in D-Mtb. Thus, our results indicate that D-Mtb cannot escape MHC class II Ag-processing pathway because it lacks the expression of genes required to block the phagosome maturation. Data suggest that switching to dormancy not only represents a mechanism of survival in latent TB infection, but also a M. tuberculosis strategy to modulate the immune response in different stages of TB.

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“…Under some circumstances the material in the bowel wall undergoes liquefaction, as may occur with tuberculosis 232 . This material then tracks to adjoining organs, possibly driven by the osmotic pressure produced by the breakdown of the organic material within the abscess, and discharges into them.…”

Section: Immunoparesis Of the Acute Inflammatory Response Is The Undementioning

confidence: 99%

Making sense of the cause of Crohn’s – a new look at an old disease

Segal

2016

F1000Res

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The cause of Crohn’s disease (CD) has posed a conundrum for at least a century. A large body of work coupled with recent technological advances in genome research have at last started to provide some of the answers. Initially this review seeks to explain and to differentiate between bowel inflammation in the primary immunodeficiencies that generally lead to very early onset diffuse bowel inflammation in humans and in animal models, and the real syndrome of CD. In the latter, a trigger, almost certainly enteric infection by one of a multitude of organisms, allows the faeces access to the tissues, at which stage the response of individuals predisposed to CD is abnormal. Direct investigation of patients’ inflammatory response together with genome-wide association studies (GWAS) and DNA sequencing indicate that in CD the failure of acute inflammation and the clearance of bacteria from the tissues, and from within cells, is defective. The retained faecal products result in the characteristic chronic granulomatous inflammation and adaptive immune response. In this review I will examine the contemporary evidence that has led to this understanding, and look for explanations for the recent dramatic increase in the incidence of this disease.

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A Spotlight on Liquefaction: Evidence from Clinical Settings and Experimental Models in Tuberculosis

Cited by 29 publications

References 55 publications

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis

Aptamer-based proteomic signature of intensive phase treatment response in pulmonary tuberculosis

Dormant Mycobacterium tuberculosis Fails To Block Phagosome Maturation and Shows Unexpected Capacity To Stimulate Specific Human T Lymphocytes

Making sense of the cause of Crohn’s – a new look at an old disease

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