Pulmonary immune responses to Mycobacterium tuberculosis in exposed individuals

Herzmann, Christian; Ernst, Martin; Lange, Christoph; Stenger, Steffen; Kaufmann, Stefan H. E.; Reiling, Norbert; Schaberg, T.; Merwe, Lize van der; Maertzdorf, Jeroen

doi:10.1371/journal.pone.0187882

Cited by 10 publications

(7 citation statements)

References 39 publications

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“…Although few if any studies have measured the BAL cell response to bacterial pathogens in CF, some have been performed for other disease states. In those cases, many have involved stimulating BAL cells with proteins, heat‐treated bacteria or bacterial lysate, 20‐22 with exceptions often being those involving slow‐growing bacteria such as mycobacteria 23 . While informative, lysing, or heat‐treating bacteria could release PAMPs, normally contained within the structure of the cell (ie LPS, peptidoglycan, lipopeptides, DNA and RNA) 24 possibly facilitating increased TLR ligand activation as compared to live bacteria.…”

Section: Discussionmentioning

confidence: 99%

“…In those cases, many have involved stimulating BAL cells with proteins, heat-treated bacteria or bacterial lysate, [20][21][22] with exceptions often being those involving slow-growing bacteria such as mycobacteria. 23 While informative, lysing, or heat-treating bacteria could release PAMPs, normally contained within the structure of the cell (ie LPS, peptidoglycan, lipopeptides, DNA and RNA) 24 possibly facilitating increased TLR ligand activation as compared to live bacteria. Hence, such stimulations might not necessarily trigger the same activation pathways in vitro, as occur with live pathogenic bacteria, as in the lung.…”

Section: Discussionmentioning

confidence: 99%

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A bacterial stimulation assay for bronchoalveolar lavage immune cells from young children with cystic fibrosis

et al. 2021

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Cystic Fibrosis (CF) is primarily a progressive lung disease, characterized by chronic pulmonary infections with opportunistic pathogens. Such infections typically commence early in life, producing an inflammatory response marked by IL‐8 chemokine production and neutrophilic infiltration, major contributory factors in CF progression. Studying this inflammation, especially early in life, is critical for developing new strategies for preventing or slowing disruption to the structural integrity of the CF airways. However, evaluating the immune responses of bronchoalveolar lavage (BAL) cells from children with CF faces technical challenges, including contamination carried from the lung due to pre‐existing infections and low cell number availability. Here, we describe a technique for preparing BAL cells from young children with CF and using those cells in a bacterial stimulation assay. Initial antibiotic treatment proved essential for preventing resident bacteria from overgrowing BAL cell cultures, or non‐specifically activating the cells. ACTB, identified as an optimal reference gene, was validated for accurate analysis of gene expression in these cells. Pseudomonas aeruginosa and Staphylococcus aureus were used as bacterial stimulants to evaluate the immune response of BAL cells from young children with CF. Addition of gentamicin prevented bacterial overgrowth, although if added after 3 hours of culture an extremely variable response resulted, with the bacteria causing a suppressive effect in some cultures. Addition of gentamicin after 1 hour of culture completely prevented this suppressive effect. This technique was then able to reproducibly measure the IL‐8 response to stimulation with S. aureus and P. aeruginosa, including co‐stimulation with both bacteria.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

A bacterial stimulation assay for bronchoalveolar lavage immune cells from young children with cystic fibrosis

et al. 2021

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“…Several studies have confirmed an overactive immune system in severe COVID-19 patients that correlates with patient mortality. Infections with TB reprogram the macrophages to secrete a distinct set of cytokines (Herzmann et al, 2017). Moreover, macrophages subpopulations have been identified to exert a possible anti-inflammatory or pro-inflammatory response that is identifiable by their distinct metabolomics signature.…”

Section: Comparison With Published Metabolomics Dataset Featuring Pro...mentioning

confidence: 99%

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2

Diboun

Cyprian

Anwardeen

et al. 2022

Front. Cell. Infect. Microbiol.

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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection currently remains one of the biggest global challenges that can lead to acute respiratory distress syndrome (CARDS) in severe cases. In line with this, prior pulmonary tuberculosis (TB) is a risk factor for long-term respiratory impairment. Post-TB lung dysfunction often goes unrecognized, despite its relatively high prevalence and its association with reduced quality of life. In this study, we used a metabolomics analysis to identify potential biomarkers that aid in the prognosis of COVID-19 morbidity and mortality in post-TB infected patients. This analysis involved blood samples from 155 SARS-CoV-2 infected adults, of which 23 had a previous diagnosis of TB (post-TB), while 132 did not have a prior or current TB infection. Our analysis indicated that the vast majority (~92%) of post-TB individuals showed severe SARS-CoV-2 infection, required intensive oxygen support with a significantly high mortality rate (52.2%). Amongst individuals with severe COVID-19 symptoms, we report a significant decline in the levels of amino acids, notably the branched chains amino acids (BCAAs), more so in the post-TB cohort (FDR <= 0.05) in comparison to mild and asymptomatic cases. Indeed, we identified betaine and BCAAs as potential prognostic metabolic biomarkers of severity and mortality, respectively, in COVID-19 patients who have been exposed to TB. Moreover, we identified serum alanine as an important metabolite at the interface of severity and mortality. Hence, our data associated COVID-19 mortality and morbidity with a long-term metabolically driven consequence of TB infection. In summary, our study provides evidence for a higher mortality rate among COVID-19 infection patients who have history of prior TB infection diagnosis, which mandates validation in larger population cohorts.

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“…In contrast, the risk to develop TB disease in these young infants was associated with an increased circulation of activated CD4 + T cells, suggesting a possible contribution of early immune activation to disease susceptibility . Intriguingly, stronger cellular responses were detected as preactivated lymphocytes and increased Th1 cytokine production but impaired macrophage activation in bronchoalveolar lavage (BAL) from individuals with latent TB compared healthy exposed individuals . The balance in protective versus pathogenic CD4 + T‐cells responses in different phases of TB infection and disease will certainly be an interesting subject for further exploration.…”

Section: Effector Cells Subsets Involved In Protective Tb Immunitymentioning

confidence: 99%

Friends and foes of tuberculosis: modulation of protective immunity

Brighenti

Joosten

2018

J Intern Med

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Protective immunity in tuberculosis (TB) is subject of debate in the TB research community, as this is key to fully understand TB pathogenesis and to develop new promising tools for TB diagnosis and prognosis as well as a more efficient TB vaccine. IFN-γ producing CD4 T cells are key in TB control, but may not be sufficient to provide protection. Additional subsets have been identified that contribute to protection such as multifunctional and cytolytic T-cell subsets, including classical and nonclassical T cells as well as novel innate immune cell subsets resulting from trained immunity. However, to define protective immune responses against TB, the complexity of balancing TB immunity also has to be considered. In this review, insights into effector cell immunity and how this is modulated by regulatory cells, associated comorbidities and the host microbiome, is discussed. We systematically map how different suppressive immune cell subsets may affect effector cell responses at the local site of infection. We also dissect how common comorbidities such as HIV, helminths and diabetes may bias protective TB immunity towards pathogenic and regulatory responses. Finally, also the composition and diversity of the microbiome in the lung and gut could affect host TB immunity. Understanding these various aspects of the immunological balance in the human host is fundamental to prevent TB infection and disease.

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Pulmonary immune responses to Mycobacterium tuberculosis in exposed individuals

Cited by 10 publications

References 39 publications

A bacterial stimulation assay for bronchoalveolar lavage immune cells from young children with cystic fibrosis

A bacterial stimulation assay for bronchoalveolar lavage immune cells from young children with cystic fibrosis

Identification of Prognostic Metabolomic Biomarkers at the Interface of Mortality and Morbidity in Pre-Existing TB Cases Infected With SARS-CoV-2

Friends and foes of tuberculosis: modulation of protective immunity

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