Local Pulmonary Immunological Biomarkers in Tuberculosis

Frontiers in Immunology ◽

10.3389/fimmu.2021.640916 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hazel Morrison ◽

Helen McShane

Keyword(s):

Peripheral Blood ◽

Bronchoalveolar Lavage Fluid ◽

Lavage Fluid ◽

Correlates Of Protection ◽

Point Of Entry ◽

Potential Applications ◽

Alternative Approaches ◽

Resident Memory T Cells ◽

Peripheral Samples

Regardless of the eventual site of disease, the point of entry for Mycobacterium tuberculosis (M.tb) is via the respiratory tract and tuberculosis (TB) remains primarily a disease of the lungs. Immunological biomarkers detected from the respiratory compartment may be of particular interest in understanding the complex immune response to M.tb infection and may more accurately reflect disease activity than those seen in peripheral samples. Studies in humans and a variety of animal models have shown that biomarkers detected in response to mycobacterial challenge are highly localized, with signals seen in respiratory samples that are absent from the peripheral blood. Increased understanding of the role of pulmonary specific biomarkers may prove particularly valuable in the field of TB vaccines. Here, development of vaccine candidates is hampered by the lack of defined correlates of protection (COPs). Assessing vaccine immunogenicity in humans has primarily focussed on detecting these potential markers of protection in peripheral blood. However, further understanding of the importance of local pulmonary immune responses suggests alternative approaches may be necessary. For example, non-circulating tissue resident memory T cells (TRM) play a key role in host mycobacterial defenses and detecting their associated biomarkers can only be achieved by interrogating respiratory samples such as bronchoalveolar lavage fluid or tissue biopsies. Here, we review what is known about pulmonary specific immunological biomarkers and discuss potential applications and further research needs.

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Crucial Role of Extracellular Vesicles in Bronchial Asthma

International Journal of Molecular Sciences ◽

10.3390/ijms20102589 ◽

2019 ◽

Vol 20 (10) ◽

pp. 2589 ◽

Cited By ~ 7

Author(s):

Tatsuya Nagano ◽

Masahiro Katsurada ◽

Ryota Dokuni ◽

Daisuke Hazama ◽

Tatsunori Kiriu ◽

...

Keyword(s):

Bronchial Asthma ◽

Extracellular Vesicles ◽

Bronchoalveolar Lavage Fluid ◽

Cell Types ◽

Lavage Fluid ◽

Generation Process ◽

Intracellular Proteins ◽

Novel Biomarkers ◽

Microarray Analyses

Extracellular vesicles (EVs) are circulating vesicles secreted by various cell types. EVs are classified into three groups according to size, structural components, and generation process of vesicles: exosomes, microvesicles, and apoptotic bodies. Recently, EVs have been considered to be crucial for cell-to-cell communications and homeostasis because they contain intracellular proteins and nucleic acids. Epithelial cells from mice suffering from bronchial asthma (BA) secrete more EVs and suppress inflammation-induced EV production. Moreover, microarray analyses of bronchoalveolar lavage fluid have revealed that several microRNAs are useful novel biomarkers of BA. Mesenchymal stromal cell-derived EVs are possible candidates of novel BA therapy. In this review, we highlight the biologic roles of EVs in BA and review novel EV-targeted therapy to help understanding by clinicians and biologists.

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Role of TNFR1 in the innate airway hyperresponsiveness of obese mice

Journal of Applied Physiology ◽

10.1152/japplphysiol.00588.2012 ◽

2012 ◽

Vol 113 (9) ◽

pp. 1476-1485 ◽

Cited By ~ 11

Author(s):

Ming Zhu ◽

Alison S. Williams ◽

Lucas Chen ◽

Allison P. Wurmbrand ◽

Erin S. Williams ◽

...

Keyword(s):

Airway Hyperresponsiveness ◽

Bronchoalveolar Lavage Fluid ◽

Pulmonary Inflammation ◽

Tumor Necrosis Factor Receptor ◽

Lavage Fluid ◽

Forced Oscillation Technique ◽

Obese Mice ◽

Wild Type ◽

Necrosis Factor

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe fat mice that were either sufficient or genetically deficient in TNFR1 ( Cpe fat and Cpe fat/TNFR1−/− mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1−/− mice]. Compared with lean WT mice, Cpe fat mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe fat/TNFR1−/− than in Cpe fat mice. Compared with WT mice, Cpe fat mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice. Additional moieties including IL-13 were also elevated in Cpe fat/TNFR1−/− vs. TNFR1−/− mice but not in Cpe fat vs. WT mice. IL-17A mRNA expression was greater in Cpe fat/TNFR1−/− vs. Cpe fat mice and in TNFR1−/− vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

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The Role of Thoracic Ultrasonography and Airway Endoscopy in the Diagnosis of Equine Asthma and Exercise-Induced Pulmonary Hemorrhage

Veterinary Sciences ◽

10.3390/vetsci8110276 ◽

2021 ◽

Vol 8 (11) ◽

pp. 276

Author(s):

Chiara Maria Lo Feudo ◽

Luca Stucchi ◽

Elena Alberti ◽

Giovanni Stancari ◽

Bianca Conturba ◽

...

Keyword(s):

Bronchoalveolar Lavage Fluid ◽

Pulmonary Hemorrhage ◽

Lavage Fluid ◽

Lymphoid Hyperplasia ◽

Inflammatory Status ◽

Equine Asthma ◽

Exercise Induced ◽

Tracheal Mucus ◽

Tracheal Bifurcation

Mild-moderate (MEA), severe (SEA) equine asthma and exercise-induced pulmonary hemorrhage (EIPH) are common respiratory disorders in horses. The present retrospective study aims to evaluate the role of ultrasonography and endoscopy in the diagnosis of these conditions. Three hundred and three horses were included and divided into SEA, MEA and MEA + EIPH groups, on the basis of history, clinical examination and bronchoalveolar lavage fluid (BALf) cytology; scores were assigned to lung ultrasonography, pharyngeal lymphoid hyperplasia (PLH), tracheal mucus (TM) and tracheal bifurcation edema (TB). These scores were compared between groups, and their associations with age, BALf cytology, tracheal wash microbiology and between endoscopic and ultrasonographic scores were statistically analyzed. Ultrasonographic scores were higher in the SEA and MEA + EIPH groups and associated with increased BALf neutrophils and hemosiderophages. The PLH score was higher in younger horses affected by MEA and EIPH and associated with increased eosinophils and hemosiderophages. TM and TB scores were greater in older horses affected by SEA, associated with increased neutrophils and inversely correlated with hemosiderophages. Moreover, TM grade was negatively correlated with mast cells. Thoracic ultrasonography and airway endoscopy can provide useful information about the inflammatory status of upper and lower airways in the horse.

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2045 The role of TGFβ in driving early cystic fibrosis lung disease

Journal of Clinical and Translational Science ◽

10.1017/cts.2018.139 ◽

2018 ◽

Vol 2 (S1) ◽

pp. 33-33

Author(s):

Elizabeth L. Kramer ◽

William Hardie ◽

Kristin Hudock ◽

Cynthia Davidson ◽

Alicia Ostmann ◽

...

Keyword(s):

Cystic Fibrosis ◽

Bronchoalveolar Lavage ◽

Lung Disease ◽

Bronchoalveolar Lavage Fluid ◽

Transforming Growth Factor ◽

Genetic Modifier ◽

Lavage Fluid ◽

Lung Mechanics ◽

Patient Specific

OBJECTIVES/SPECIFIC AIMS: Transforming growth factor-beta (TGFβ) is a genetic modifier of cystic fibrosis (CF) lung disease. TGFβ’s pulmonary levels in young CF patients and its mechanism of action in CF are unknown. We examined TGFβ levels in children with CF and investigated responses of human airway epithelial cells (AECs) and mice to TGFβ. METHODS/STUDY POPULATION: TGFβ levels in bronchoalveolar lavage fluid from CF patients (n=15) and non-CF control patients (n=21)<6 years old were determined by ELISA. CF mice and non-CF mice were intratracheally treated with an adenoviral TGFβ1 vector or PBS; lungs were collected for analysis at day 7. Human CF and non-CF AECs were treated with TGFβ or PBS for 24 hours then collected for analysis. RESULTS/ANTICIPATED RESULTS: Young CF patients had higher bronchoalveolar lavage fluid TGFβ than non-CF controls (p=0.03). Mouse lungs exposed to TGFβ demonstrated inflammation, goblet cell hyperplasia, and decreased CFTR expression. CF mice had greater TGFβ-induced lung mechanics abnormalities than controls; both CF human AECs and CF mice showed higher TGFβ induced MAPK and PI3K signaling compared with controls. DISCUSSION/SIGNIFICANCE OF IMPACT: For the first time, we show increased TGFβ levels very early in CF. TGFβ drives CF lung abnormalities in mouse and human models; CF models are more sensitive to TGFβ’s effects. Understanding the role of TGFβ in promoting CF lung disease is critical to developing patient specific treatments.

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