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Cell Death & Disease Sep 2018Infection with Influenza A virus (IAV) causes significant cell death within the upper and lower respiratory tract and lung parenchyma. In severe infections, high levels... (Review)
Review
Infection with Influenza A virus (IAV) causes significant cell death within the upper and lower respiratory tract and lung parenchyma. In severe infections, high levels of cell death can exacerbate inflammation and comprise the integrity of the epithelial cell barrier leading to respiratory failure. IAV infection of airway and alveolar epithelial cells promotes immune cell infiltration into the lung and therefore, immune cell types such as macrophages, monocytes and neutrophils are readily exposed to IAV and infection-induced death. Although the induction of cell death through apoptosis and necrosis following IAV infection is a well-known phenomenon, the molecular determinants responsible for inducing cell death is not fully understood. Here, we review the current understanding of IAV-induced cell death and critically evaluate the consequences of cell death in aiding either the restoration of lung homoeostasis or the progression of IAV-induced lung pathologies.
Topics: Alveolar Epithelial Cells; Animals; Apoptosis; Cell Death; Humans; Inflammation; Influenza A virus; Influenza, Human; Lung; Macrophages; Neutrophils; Orthomyxoviridae Infections
PubMed: 30254192
DOI: 10.1038/s41419-018-1035-6 -
Journal of Thoracic Imaging Sep 2018Pulmonary infections in immunocompromised patients remain a significant contributor to mortality, morbidity, and health care-associated costs in such a vulnerable... (Review)
Review
Pulmonary infections in immunocompromised patients remain a significant contributor to mortality, morbidity, and health care-associated costs in such a vulnerable patient population. Their epidemiology is changing, set forth by new trends in immunosuppressive regimens and also prophylaxis. The host characteristics, presenting clinical symptomatology, along with radiographic patterns, have also evolved. The microbiology diagnostics are now enriched with nonculture methods for better identification of the causative pathogens. Chest imaging remains the cornerstone of the initial workup. Our article will examine the new trends in epidemiology, clinical findings, and diagnostics for immunocompromised patients with pulmonary infections (transplant recipients, neutropenic hosts, HIV-infected patients, and patients with autoimmune conditions). We will also review the differential diagnosis that most of the times includes malignancies and drug or radiation-related toxicities.
Topics: Humans; Immunocompromised Host; Lung; Respiratory Tract Infections; Risk Factors
PubMed: 30048345
DOI: 10.1097/RTI.0000000000000351 -
European Respiratory Review : An... Mar 2018Over the past year, studies into virus-induced wheeze in children have shifted towards investigations that examine the mechanisms by which respiratory viruses cause... (Review)
Review
Over the past year, studies into virus-induced wheeze in children have shifted towards investigations that examine the mechanisms by which respiratory viruses cause wheeze and an increase in studies examining the effects of novel interventions to reduce wheezing exacerbations. Studies on rhinovirus species (RV)-C infection have found that this is associated with a decrease in expression of CDHR3, the cellular receptor specific for this virus, and a decrease in interferon-β expression, both of which are likely to favour RV-C infection. Recent clinical trials in children have found a decrease in wheezing exacerbations with both anti-respiratory syncytial virus antibody and anti-immunoglobulin E antibody therapy, and a clinical trial of prednisolone in children with their first RV-induced wheeze showed that only those with an RV viral count >7000 copies·mL responded. Further studies on the effects of bacterial lysates on immune system function continue to support the potential of this approach to reduce virus-induced wheezing exacerbations in children. These studies and many previous investigations into immunomodulation using bacterial lysates have led to the funding and commencement of a large study in which long-term administration of a bacterial lysate in young children will be assessed for its ability to prevent asthma.
Topics: Adjuvants, Immunologic; Antiviral Agents; Biological Products; Glucocorticoids; Host-Pathogen Interactions; Humans; Immunization; Lung; Respiratory Sounds; Respiratory Tract Infections; Risk Factors; Treatment Outcome; Viral Load; Viral Vaccines; Virus Diseases; Viruses
PubMed: 29622672
DOI: 10.1183/16000617.0133-2017 -
Journal of Molecular Cell Biology Jul 2021The high infectivity and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused the COVID-19 outbreak, one of the most devastating... (Review)
Review
The high infectivity and pathogenicity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused the COVID-19 outbreak, one of the most devastating pandemics in more than a century. This pandemic has already left a trail of destruction, including enormous loss of life, a global economic slump, and widespread psychological damage. Despite assiduous world-wide endeavors, an effective cure for COVID-19 is still lacking. Surprisingly, infected neonates and children have relatively mild clinical manifestations and a much lower fatality rate than elderly adults. Recent studies have unambiguously demonstrated the vertical transmission of SARS-CoV-2 from infected pregnant women to fetuses, which creates yet another challenge for disease prevention. In this review, we will summarize the molecular mechanism for entry of SARS-CoV-2 into host cells, the basis for the failure of the lungs and other organs in severe acute cases, and the evidence for congenital transmission.
Topics: COVID-19; Female; Fetus; Humans; Infectious Disease Transmission, Vertical; Lung; Pandemics; Pregnancy; SARS-CoV-2; Virus Internalization
PubMed: 33677567
DOI: 10.1093/jmcb/mjab013 -
Marine Drugs Dec 2020Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that... (Review)
Review
Compromised lung function is a feature of both infection driven and non-infective pathologies. Viral infections-including the current pandemic strain SARS-CoV-2-that affect lung function can cause both acute and long-term chronic damage. SARS-CoV-2 infection suppresses innate immunity and promotes an inflammatory response. Targeting these aspects of SARS-CoV-2 is important as the pandemic affects greater proportions of the population. In clinical and animal studies, fucoidans have been shown to increase innate immunity and decrease inflammation. In addition, dietary fucoidan has been shown to attenuate pulmonary damage in a model of acute viral infection. Direct inhibition of SARS-CoV-2 in vitro has been described, but is not universal. This short review summarizes the current research on fucoidan with regard to viral lung infections and lung damage.
Topics: Animals; COVID-19; Humans; Lung; Lung Diseases; Polysaccharides; SARS-CoV-2; Virus Diseases; COVID-19 Drug Treatment
PubMed: 33374149
DOI: 10.3390/md19010004 -
International Journal of Molecular... Apr 2024Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of... (Review)
Review
Despite the end of the pandemic, coronavirus disease 2019 (COVID-19) remains a major public health concern. The first waves of the virus led to a better understanding of its pathogenesis, highlighting the fact that there is a specific pulmonary vascular disorder. Indeed, COVID-19 may predispose patients to thrombotic disease in both venous and arterial circulation, and many cases of severe acute pulmonary embolism have been reported. The demonstrated presence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) within the endothelial cells suggests that direct viral effects, in addition to indirect effects of perivascular inflammation and coagulopathy, may contribute to pulmonary vasculopathy in COVID-19. In this review, we discuss the pathological mechanisms leading to pulmonary vascular damage during acute infection, which appear to be mainly related to thromboembolic events, an impaired coagulation cascade, micro- and macrovascular thrombosis, endotheliitis and hypoxic pulmonary vasoconstriction. As many patients develop post-COVID symptoms, including dyspnea, we also discuss the hypothesis of pulmonary vascular damage and pulmonary hypertension as a sequela of the infection, which may be involved in the pathophysiology of long COVID.
Topics: Humans; COVID-19; SARS-CoV-2; Lung; Pulmonary Embolism; Hypertension, Pulmonary; Post-Acute COVID-19 Syndrome; Thrombosis
PubMed: 38732160
DOI: 10.3390/ijms25094941 -
International Journal of Infectious... Oct 2016Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of... (Review)
Review
BACKGROUND
Acute and chronic respiratory tract infections are a common cause of inappropriate antimicrobial prescription. Antimicrobial therapy leads to the development of resistance and the emergence of opportunistic pathogens that substitute the indigenous microbiota.
METHODS
This review explores the major challenges and lines of research to adequately establish the clinical role of bacteria and the indications for antimicrobial treatment, and reviews novel therapeutic approaches.
RESULTS
In patients with chronic pulmonary diseases and structural disturbances of the bronchial tree or the lung parenchyma, clinical and radiographic signs and symptoms are almost constantly present, including a basal inflammatory response. Bacterial adaptative changes and differential phenotypes are described, depending on the clinical role and niche occupied. The respiratory tract has areas that are potentially inaccessible to antimicrobials. Novel therapeutic approaches include new ways of administering antimicrobials that may allow intracellular delivery or delivery across biofilms, targeting the functions essential for infection, such as regulatory systems, or the virulence factors required to cause host damage and disease. Alternatives to antibiotics and antimicrobial adjuvants are under development.
CONCLUSIONS
Prudent treatment, novel targets, and improved drug delivery systems will contribute to reduce the emergence of antimicrobial resistance in lower respiratory tract infections.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Biofilms; Drug Carriers; Drug Delivery Systems; Host-Pathogen Interactions; Humans; Lung; Microbiota; Phage Therapy; Respiratory Tract Infections; Virulence Factors
PubMed: 27776777
DOI: 10.1016/j.ijid.2016.09.005 -
Seminars in Diagnostic Pathology Nov 2017
Review
Topics: Bacteria; Bacteriological Techniques; Biopsy; Host-Pathogen Interactions; Humans; Lung; Pneumonia, Bacterial; Predictive Value of Tests; Tomography, X-Ray Computed
PubMed: 28655479
DOI: 10.1053/j.semdp.2017.06.001 -
Nature May 2021Recent studies have provided insights into the pathology of and immune response to COVID-19. However, a thorough investigation of the interplay between infected cells...
Recent studies have provided insights into the pathology of and immune response to COVID-19. However, a thorough investigation of the interplay between infected cells and the immune system at sites of infection has been lacking. Here we use high-parameter imaging mass cytometry that targets the expression of 36 proteins to investigate the cellular composition and spatial architecture of acute lung injury in humans (including injuries derived from SARS-CoV-2 infection) at single-cell resolution. These spatially resolved single-cell data unravel the disordered structure of the infected and injured lung, alongside the distribution of extensive immune infiltration. Neutrophil and macrophage infiltration are hallmarks of bacterial pneumonia and COVID-19, respectively. We provide evidence that SARS-CoV-2 infects predominantly alveolar epithelial cells and induces a localized hyperinflammatory cell state that is associated with lung damage. We leverage the temporal range of fatal outcomes of COVID-19 in relation to the onset of symptoms, which reveals increased macrophage extravasation and increased numbers of mesenchymal cells and fibroblasts concomitant with increased proximity between these cell types as the disease progresses-possibly as a result of attempts to repair the damaged lung tissue. Our data enable us to develop a biologically interpretable landscape of lung pathology from a structural, immunological and clinical standpoint. We use this landscape to characterize the pathophysiology of the human lung from its macroscopic presentation to the single-cell level, which provides an important basis for understanding COVID-19 and lung pathology in general.
Topics: Alveolar Epithelial Cells; COVID-19; Disease Progression; Humans; Inflammation; Lung; Macrophages; Neutrophils; SARS-CoV-2; Single-Cell Analysis; Time Factors; Viral Tropism
PubMed: 33780969
DOI: 10.1038/s41586-021-03475-6 -
European Respiratory Review : An... Jun 2019Idiopathic pulmonary fibrosis (IPF) arises in genetically susceptible individuals as a result of an aberrant wound-healing response following repetitive alveolar injury.... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) arises in genetically susceptible individuals as a result of an aberrant wound-healing response following repetitive alveolar injury. The clinical course of the disease remains both variable and unpredictable with periods of more rapid decline, termed acute exacerbation of IPF (AE-IPF), often punctuating the disease trajectory. Exacerbations carry a significant morbidity and mortality, and their exact pathogenesis remains unclear. Given the emerging evidence that disruption and alteration in the lung microbiome plays a role in the pathogenesis and progression of IPF, this review discusses the current knowledge of the contribution of infection and the respiratory microbiome to AE-IPF.
Topics: Animals; Bacteria; Disease Progression; Dysbiosis; Host-Pathogen Interactions; Humans; Idiopathic Pulmonary Fibrosis; Lung; Microbiota; Respiratory Tract Infections
PubMed: 31285290
DOI: 10.1183/16000617.0045-2019