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Pleural macrophages translocate to the lung during infection to promote improved influenza outcomes.Proceedings of the National Academy of... Dec 2023Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and...
Seasonal influenza results in 3 to 5 million cases of severe disease and 250,000 to 500,000 deaths annually. Macrophages have been implicated in both the resolution and progression of the disease, but the drivers of these outcomes are poorly understood. We probed mouse lung transcriptomic datasets using the Digital Cell Quantifier algorithm to predict immune cell subsets that correlated with mild or severe influenza A virus (IAV) infection outcomes. We identified a unique lung macrophage population that transcriptionally resembled small serosal cavity macrophages and whose presence correlated with mild disease. Until now, the study of serosal macrophage translocation in the context of viral infections has been neglected. Here, we show that pleural macrophages (PMs) migrate from the pleural cavity to the lung after infection with IAV. We found that the depletion of PMs increased morbidity and pulmonary inflammation. There were increased proinflammatory cytokines in the pleural cavity and an influx of neutrophils within the lung. Our results show that PMs are recruited to the lung during IAV infection and contribute to recovery from influenza. This study expands our knowledge of PM plasticity and identifies a source of lung macrophages independent of monocyte recruitment and local proliferation.
Topics: Animals; Mice; Humans; Influenza, Human; Orthomyxoviridae Infections; Lung; Macrophages; Macrophages, Alveolar; Influenza A virus
PubMed: 38100417
DOI: 10.1073/pnas.2300474120 -
Cancers Mar 2022Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they... (Review)
Review
Pleural effusions are a common respiratory condition with many etiologies. Nonmalignant etiologies explain most pleural effusions and despite being nonmalignant, they can be associated with poor survival; thus, it is important to understand their pathophysiology. Furthermore, diagnosing a benign pleural pathology always harbors the uncertainty of a false-negative diagnosis for physicians and pathologists, especially for the group of non-specific pleuritis. This review aims to present the role of the inflammation in the development of benign pleural effusions, with a special interest in their pathophysiology and their association with malignancy.
PubMed: 35326567
DOI: 10.3390/cancers14061415 -
Frontiers in Immunology 2023Tuberculosis (TB) is caused by () and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in...
BACKGROUND
Tuberculosis (TB) is caused by () and remains a major health threat worldwide. However, a detailed understanding of the immune cells and inflammatory mediators in -infected tissues is still lacking. Tuberculous pleural effusion (TPE), which is characterized by an influx of immune cells to the pleural space, is thus a suitable platform for dissecting complex tissue responses to infection.
METHODS
We employed singe-cell RNA sequencing to 10 pleural fluid (PF) samples from 6 patients with TPE and 4 non-TPEs including 2 samples from patients with TSPE (transudative pleural effusion) and 2 samples with MPE (malignant pleural effusion).
RESULT
Compared to TSPE and MPE, TPE displayed obvious difference in the abundance of major cell types (e.g., NK, CD4+T, Macrophages), which showed notable associations with disease type. Further analyses revealed that the CD4 lymphocyte population in TPE favored a Th1 and Th17 response. Tumor necrosis factors (TNF)-, and XIAP related factor 1 (XAF1)-pathways induced T cell apoptosis in patients with TPE. Immune exhaustion in NK cells was an important feature in TPE. Myeloid cells in TPE displayed stronger functional capacity for phagocytosis, antigen presentation and IFN-γ response, than TSPE and MPE. Systemic elevation of inflammatory response genes and pro-inflammatory cytokines were mainly driven by macrophages in patients with TPE.
CONCLUSION
We provide a tissue immune landscape of PF immune cells, and revealed a distinct local immune response in TPE and non-TPE (TSPE and MPE). These findings will improve our understanding of local TB immunopathogenesis and provide potential targets for TB therapy.
Topics: Humans; Pleural Effusion; Tuberculosis; Antigen Presentation; Mycobacterium tuberculosis; Pleural Cavity
PubMed: 37435066
DOI: 10.3389/fimmu.2023.1191357 -
International Journal of General... 2021Pleural infection in adults has considerable morbidity and continues to be a life-threatening condition. The term "pleural infection" encompasses complicated... (Review)
Review
Pleural infection in adults has considerable morbidity and continues to be a life-threatening condition. The term "pleural infection" encompasses complicated parapneumonic effusions and primary pleural infections, and includes but is not limited to empyema, which refers to collection of pus in the pleural cavity. The incidence of pleural infection in adults has been continuously increasing over the past two decades, particularly in older adults, and most of such patients have comorbidities. Management of pleural infection requires prolonged duration of hospitalization (average 14 days). There are recognized differences in microbial etiology of pleural infection depending on whether the infection was acquired in the community or in a health-care setting. Anaerobic bacteria are acknowledged as a major cause of pleural infection, and thus anaerobic coverage in antibiotic regimens for pleural infection is mandatory. The key components of managing pleural infection are appropriate antimicrobial therapy and chest-tube drainage. In patients who fail medical therapy by manifesting persistent sepsis despite standard measures, surgical intervention to clear the infected space or intrapleural fibrinolytic therapy (in poor surgical candidates) are recommended. Recent studies have explored the role of early intrapleural fibrinolytics or first-line surgery, but due to considerable costs of such interventions and the lack of convincing evidence of improved outcomes with early use, early intervention cannot be recommended, and further evidence is awaited from ongoing studies. Other areas of research include the role of routine molecular testing of infected pleural fluid in improving the rate of identification of causative organisms. Other research topics include the benefit of such interventions as medical thoracoscopy, high-volume pleural irrigation with saline/antiseptic solution, and repeated thoracentesis (as opposed to chest-tube drainage) in reducing morbidity and improving outcomes of pleural infection. This review summarizes current knowledge and practice in managing pleural infection and future research directions.
PubMed: 34290522
DOI: 10.2147/IJGM.S292705 -
PloS One 2022Pleural mesothelial cells are the predominant cell type in the pleural cavity, but their role in the pathogenesis of pleural diseases needs to be further elucidated. 3D...
Pleural mesothelial cells are the predominant cell type in the pleural cavity, but their role in the pathogenesis of pleural diseases needs to be further elucidated. 3D organotypic models are an encouraging approach for an in vivo understanding of molecular disease development. The aim of the present study was to develop a 3D organotypic model of the pleural mesothelium. Specimens of human pleura parietalis were obtained from patients undergoing surgery at the University Hospital Leipzig, Germany. 3D co-culture model of pleura was established from human pleural mesothelial cells and fibroblasts. The model was compared to human pleura tissue by phase-contrast and light microscopy, immunochemistry and -fluorescence as well as solute permeation test. Histological assessment of the 3D co-culture model displayed the presence of both cell types mimicking the morphology of the human pleura. Vimentin and Cytokeratin, PHD1 showed a similar expression pattern in pleural biopsies and 3D model. Expression of Ki-67 indicates the presence of proliferating cells. Tight junctional marker ZO-1 was found localized at contact zones between mesothelial cells. Each of these markers were expressed in both the 3D co-culture model and human biopsies. Permeability of 3D organotypic co-culture model of pleura was found to be higher for 70 kDa-Dextran and no significant difference was seen in the permeability for small dextran (4 kDa). In summary, the presented 3D organoid of pleura functions as a robust assay for pleural research serving as a precise reproduction of the in vivo morphology and microenvironment.
Topics: Humans; Pleura; Coculture Techniques; Dextrans; Pleural Diseases; Pleural Cavity
PubMed: 36454800
DOI: 10.1371/journal.pone.0276978 -
Cancers Aug 2021Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The... (Review)
Review
Mesothelioma is a cancer predominantly of the pleural cavity. There is a clear association of exposure to asbestos with a dose dependent risk of mesothelioma. The incidence of mesothelioma in different countries reflect the historical patterns of commercial asbestos utilisation in the last century and predominant occupational exposures mean that mesothelioma is mostly seen in males. Modern imaging techniques and advances in immunohistochemical staining have contributed to an improved diagnosis of mesothelioma. There have also been recent advances in immune checkpoint inhibition, however, mesothelioma remains very challenging to manage, especially considering its limited response to conventional systemic anticancer therapy and that no cure exists. Palliative interventions and support remain paramount with a median survival of 9-12 months after diagnosis. The epidemiology and diagnosis of mesothelioma has been debated over previous decades, due to a number of factors, such as the long latent period following asbestos exposure and disease occurrence, the different potencies of the various forms of asbestos used commercially, the occurrence of mesothelioma in the peritoneal cavity and its heterogeneous pathological and cytological appearances. This review will describe the contemporary knowledge on the epidemiology of mesothelioma and provide an overview of the best clinical practice including diagnostic approaches and management.
PubMed: 34439349
DOI: 10.3390/cancers13164194 -
Diseases of Aquatic Organisms Aug 2023Pneumothorax, the accumulation of air in the pleural cavity, occurs when air enters the pleural space by the pleuro-cutaneous, pleuro-pulmonary, or...
Pneumothorax, the accumulation of air in the pleural cavity, occurs when air enters the pleural space by the pleuro-cutaneous, pleuro-pulmonary, or pleuro-oesophageal-mediastinal route. Tension pneumothorax is an infrequent and severe form of pneumothorax where a positive pressure in the pleural space is built up during at least part of the respiratory cycle, with compression of both lungs and mediastinal vessels, and, if unilateral, with midline deviation towards the unaffected hemithorax. We describe 9 cases of tension pneumothorax in 3 species of small cetaceans (striped dolphin Stenella coeruleoalba, common dolphin Delphinus delphis, and common bottlenose dolphin Tursiops truncatus) from the western Mediterranean coast of Spain, and one case from a dolphinarium. Computed tomography (CT) imaging performed in 2 carcasses before necropsy showed lung compression, midline deviation, and pressure on the diaphragm, which was caudally displaced. Tension pneumothorax was recognized at necropsy by the presence of pressurized air in one of the hemithoraces. Seven of the pneumothorax cases were spontaneous (2 primary and 5 secondary to previous lung pathology). In the other 2 dolphins, the pneumothorax was traumatic, due to oesophageal-pleural perforation or rib fractures. We hypothesize that pneumothorax in dolphins is predominantly tensional because of their specific anatomical and physiological adaptations to marine life and the obligate exposure to extreme pressure changes as diving mammals.
Topics: Animals; Pneumothorax; Stenella; Cetacea; Bottle-Nosed Dolphin; Common Dolphins
PubMed: 37534721
DOI: 10.3354/dao03741 -
Biology Mar 2022Lymphatic vessels exploit the mechanical stresses of their surroundings together with intrinsic rhythmic contractions to drain lymph from interstitial spaces and serosal... (Review)
Review
Lymphatic vessels exploit the mechanical stresses of their surroundings together with intrinsic rhythmic contractions to drain lymph from interstitial spaces and serosal cavities to eventually empty into the blood venous stream. This task is more difficult when the liquid to be drained has a very subatmospheric pressure, as it occurs in the pleural cavity. This peculiar space must maintain a very low fluid volume at negative hydraulic pressure in order to guarantee a proper mechanical coupling between the chest wall and lungs. To better understand the potential for liquid drainage, the key parameter to be considered is the difference in hydraulic pressure between the pleural space and the lymphatic lumen. In this review we collected old and new findings from in vivo direct measurements of hydraulic pressures in anaesthetized animals with the aim to better frame the complex physiology of diaphragmatic and intercostal lymphatics which drain liquid from the pleural cavity.
PubMed: 35336793
DOI: 10.3390/biology11030419 -
Thorax Nov 2021Infection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a...
BACKGROUND
Infection of the pleural cavity invariably leads to hospitalisation, and a fatal outcome is not uncommon. Our aim was to study the epidemiology of pleural empyema on a nationwide basis in the whole population and in three subgroups of patients, namely post-lung resection, associated cancer and those with no surgery and no cancer.
METHODS
Data from patients aged ≥18 years hospitalised with a diagnosis of pleural infection in France between January 2013 and December 2017 were retrieved from the medical-administrative national hospitalisation database and retrospectively analysed. Mortality, length of stay and costs were assessed.
RESULTS
There were 25 512 hospitalisations for pleural empyema. The annual rate was 7.15 cases per 100 000 habitants in 2013 and increased to 7.75 cases per 100 000 inhabitants in 2017. The mean age of patients was 62.4±15.6 years and 71.7% were men. Post-lung resection, associated cancer and no surgery-no cancer cases accounted for 9.8%, 30.1% and 60.1% of patients, respectively. These groups were significantly different in terms of clinical characteristics, mortality and risk factors for length of stay, costs and mortality. Mortality was 17.1% in the whole population, 29.5% in the associated cancer group, 17.7% in the post-lung resection group and 10.7% in the no surgery-no cancer group. In the whole population, age, presence of fistula, higher Charlson Comorbidity Index (3), alcohol abuse, arterial hypertension, hyperlipidaemia, atheroma, atrial fibrillation, performance status 3 and three subgroups of pleural empyema independently predicted mortality.
CONCLUSIONS
Empyema is increasing in incidence. Factors associated with mortality are recent lung resection and associated diagnosis of cancer.
Topics: Adolescent; Adult; Aged; Empyema, Pleural; Humans; Incidence; Male; Middle Aged; Pleural Diseases; Prognosis; Retrospective Studies
PubMed: 33785584
DOI: 10.1136/thoraxjnl-2020-215267 -
Frontiers in Cellular and Infection... 2022Pancreaticopleural fistula (PPF) is a serious complication of acute and chronic pancreatitis.
INTRODUCTION
Pancreaticopleural fistula (PPF) is a serious complication of acute and chronic pancreatitis.
OBJECTIVE
To evaluate the effectiveness of various endoscopic techniques for the treatment of patients with PPFs.
METHODOLOGY
Prospective analysis of the results of endoscopic treatment of 22 patients with PPF due to pancreatitis was conducted at the Department of General, Gastroenterological, and Oncological Surgery, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, between 2018 and 2021.
RESULTS
PPF was diagnosed in 22 patients (21 men and 1 woman; mean age 49.52 [30-67] years) with pancreatitis. In 19/22 (86.36%) patients, PPF communicated with the left pleural cavity and in 3/22 (13.64%) patients with the right pleural cavity. Chronic pancreatitis was diagnosed in 14/22 (63.64%) patients. Symptomatic pancreatic fluid collections were found in 15/22 (68.18%) patients with PPF (pancreatic pseudocyst in 11 and walled-off pancreatic necrosis in four patients). Endoscopic retrograde cholangiopancreatography was performed in 21/22 (95.45%) patients, confirming the diagnosis of PPF. All 21 patients underwent endoscopic sphincterotomy with prosthesis implantation in the main pancreatic duct (passive transpapillary drainage). In 1/22 (4.55%) patients, active transmural/transgastric drainage of the PPF was necessary due to inflammatory infiltration of the peripapillary region, precluding endoscopic pancreatography. Endoscopic transmural drainage was performed in all the 15 patients with pancreatic fluid collection. Clinical success was achieved in 21/22 (95.45%) patients. The mean total time of endotherapy was 191 (range 88-712) days. Long-term success of endoscopic treatment of PPFs during one year follow-up period was achieved in 19/22 (86.36%) patients.
CONCLUSIONS
Endoscopic treatment is effective for managing post-inflammatory PPFs. The preferred treatment method is passive transpapillary drainage (prosthesis of the main pancreatic duct). If transpapillary drainage is not feasible, transmural drainage of the PPF remains the preferred method. Endoscopic transmural drainage leads to closure of the fistula canal in patients with pancreatic fluid collection complicated by PPF.
Topics: Male; Female; Humans; Middle Aged; Treatment Outcome; Pancreatitis, Acute Necrotizing; Cholangiopancreatography, Endoscopic Retrograde; Fistula; Pancreatitis, Chronic; Retrospective Studies
PubMed: 36262187
DOI: 10.3389/fcimb.2022.939137