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Viruses May 2020Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become... (Review)
Review
Viruses are the most common cause of acute respiratory tract infections (ARTI). Human metapneumovirus (hMPV) frequently causes viral pneumonia which can become life-threatening if the virus spreads to the lungs. Even though hMPV was only isolated in 2001, this negative-stranded RNA virus has probably been circulating in the human population for many decades. Interestingly, almost all adults have serologic evidence of hMPV infection. A well-established host immune response is evoked when hMPV infection occurs. However, the virus has evolved to circumvent and even exploit the host immune response. Further, infection with hMPV induces a weak memory response, and re-infections during life are common. In this review, we provide a comprehensive overview of the different cell types involved in the immune response in order to better understand the immunopathology induced by hMPV. Such knowledge may contribute to the development of vaccines and therapeutics directed against hMPV.
Topics: Humans; Immune Evasion; Immunity, Cellular; Immunity, Innate; Lung; Metapneumovirus; Paramyxoviridae Infections; Respiratory Tract Infections; Virus Replication
PubMed: 32423043
DOI: 10.3390/v12050542 -
American Journal of Physiology. Lung... Aug 2020In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early... (Review)
Review
In the last few months, the number of cases of a new coronavirus-related disease (COVID-19) rose exponentially, reaching the status of a pandemic. Interestingly, early imaging studies documented that pulmonary vascular thickening was specifically associated with COVID-19 pneumonia, implying a potential tropism of the virus for the pulmonary vasculature. Moreover, SARS-CoV-2 infection is associated with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, DNA damage, and lung coagulopathy promoting endothelial dysfunction and microthrombosis. These features are strikingly similar to what is seen in pulmonary vascular diseases. Although the consequences of COVID-19 on the pulmonary circulation remain to be explored, several viruses have been previously thought to be involved in the development of pulmonary vascular diseases. Patients with preexisting pulmonary vascular diseases also appear at increased risk of morbidity and mortality. The present article reviews the molecular factors shared by coronavirus infection and pulmonary vasculature defects, and the clinical relevance of pulmonary vascular alterations in the context of COVID-19.
Topics: Angiotensin-Converting Enzyme 2; Betacoronavirus; COVID-19; Coronavirus Infections; Cytokines; DNA Damage; Heart Injuries; Host Microbial Interactions; Humans; Hypoxia; Inflammation Mediators; Lung; Lung Diseases; Mitochondria; Myocardium; Oxidative Stress; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Pulmonary Circulation; Pulmonary Embolism; Receptors, Virus; Risk Factors; SARS-CoV-2; Vasculitis
PubMed: 32551862
DOI: 10.1152/ajplung.00195.2020 -
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 -
Expert Review of Respiratory Medicine Dec 2010Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin and progression that primarily affects older adults. Accumulating clinical and experimental evidence... (Review)
Review
Idiopathic pulmonary fibrosis (IPF) is a disease of unknown origin and progression that primarily affects older adults. Accumulating clinical and experimental evidence suggests that viral infections may play a role, either as agents that predispose the lung to fibrosis or exacerbate existing fibrosis. In particular, herpesviruses have been linked with IPF. This article summarizes the evidence for and against viral cofactors in IPF pathogenesis. In addition, we review mechanistic studies in animal models that highlight the fibrotic potential of viral infection, and explore the different mechanisms that might be responsible. We also review early evidence to suggest that the aged lung may be particularly susceptible to viral-induced fibrosis and make recommendations for future research directions.
Topics: Age Factors; Aging; Animals; Cellular Senescence; Disease Models, Animal; Gammaherpesvirinae; Herpesviridae Infections; Humans; Idiopathic Pulmonary Fibrosis; Lung; Risk Assessment; Risk Factors; Virus Diseases
PubMed: 21128751
DOI: 10.1586/ers.10.73 -
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 -
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 -
Viruses Jan 2022Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are...
Porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus (PCVs) are two major viruses that affect pigs. Coinfections between PRRSV and PCV2 are frequently reported in most outbreaks, with clinical presentations involving dyspnea, fever, reduced feed intake, weight loss, and death in fattening pigs. The NADC30-like PRRSV and PCV2d are the main circulating virus strains found in China. This study determines the impact of NADC30-like PRRSV and PCV2d mono-infection and coinfection on the immune system, organ pathology, and viral shedding in five-week-old post-weaned pigs. Pigs were randomly divided into six groups: PBS, PRRSV, PCV2, PRRSV-PCV2 coinfection (co), and PRRSV-PCV2 or PCV2-PRRSV sequential infections. Fever, dyspnea, decreased feed intake, weight loss, and pig deaths occurred in groups infected with PRRSV, Co-PRRSV-PCV2, and PRRSV-PCV2. The viral load was higher in Co-PRRSV-PCV2, PRRSV-PCV2, and PCV2-PRRSV than those mono-infected with PRRSV or PCV2. Additionally, cytokines (IFN-γ, TNF-α, IL-4, and IL-10) produced by pigs under Co-PRRSV-PCV2 and PRRSV-PCV2 groups were more intense than the other groups. Necropsy findings showed hemorrhage, emphysema, and pulmonary adhesions in the lungs of pigs infected with PRRSV. Smaller alveoli and widened lung interstitium were found in the Co-PRRSV-PCV2 and PRRSV-PCV2 groups. In conclusion, PRRSV and PCV2 coinfection and sequential infection significantly increased viral pathogenicity and cytokine responses, resulting in severe clinical signs, lung pathology, and death.
Topics: Animals; China; Circoviridae Infections; Circovirus; Coinfection; Female; Interleukin-10; Interleukin-4; Lung; Male; Porcine Reproductive and Respiratory Syndrome; Porcine respiratory and reproductive syndrome virus; Swine; Virulence
PubMed: 35215787
DOI: 10.3390/v14020193 -
Translational Research : the Journal of... Jan 2017The lung microbiome plays a significant role in normal lung function and disease. Because microbial colonization is likely influenced by immunodeficiency, one would... (Review)
Review
The lung microbiome plays a significant role in normal lung function and disease. Because microbial colonization is likely influenced by immunodeficiency, one would speculate that infection with human immunodeficiency virus (HIV) alters the lung microbiome. Furthermore, how this alteration might impact pulmonary complications now seen in HIV-infected patients on antiretroviral therapy (ART), which has shifted from opportunistic infections to diseases associated with chronic inflammation, is not known. There have been limited publications on the lung microbiome in HIV infection, many of them emanating from the Lung HIV Microbiome Project. Current evidence suggests that the lung microbiome in healthy HIV-infected individuals with preserved CD4 counts is similar to uninfected individuals. However, in individuals with more advanced disease, there is an altered alveolar microbiome characterized by a loss of richness and evenness (alpha diversity) within individuals. Furthermore, as a group the taxa making up the HIV-infected and uninfected lung microbiome are different (differences in beta diversity), and the HIV-infected population is more spread out (greater dispersion) than the uninfected population. These differences decline with ART, but even after effective therapy the alveolar microbiome in HIV-infected individuals contains increased amounts of signature bacteria, some of which have previously been associated with chronic lung inflammation. Furthermore, more recent investigations into the lung virome in HIV infection suggest that perturbations in lung viral communities also exist in HIV infection, and that these too are associated with evidence of lung inflammation. Thus, it is likely both microbiome and virome alterations in HIV infection contribute to lung inflammation in these individuals, which has important implications on the changing spectrum of pulmonary complications in patients living with HIV.
Topics: HIV Infections; Humans; Lung; Microbiota; Pneumonia; Treatment Outcome
PubMed: 27496318
DOI: 10.1016/j.trsl.2016.07.008 -
Current Genetics Feb 2016Many bacterial pathogens have evolved ingenious ways to escape from the lung during pneumonia to cause bacteremia. Unfortunately, the clinical consequences of this... (Review)
Review
Many bacterial pathogens have evolved ingenious ways to escape from the lung during pneumonia to cause bacteremia. Unfortunately, the clinical consequences of this spread to the bloodstream are frequently dire. It is therefore important to understand the molecular mechanisms used by pathogens to breach the lung barrier. We have recently shown that Pseudomonas aeruginosa, one of the leading causes of hospital-acquired pneumonia, utilizes the type III secretion system effector ExoS to intoxicate pulmonary epithelial cells. Injection of these cells leads to localized disruption of the pulmonary-vascular barrier and dissemination of P. aeruginosa to the bloodstream. We put these data in the context of previous studies to provide a holistic model of P. aeruginosa dissemination from the lung. Finally, we compare P. aeruginosa dissemination to that of other bacteria to highlight the complexity of bacterial pneumonia. Although respiratory pathogens use distinct and intricate strategies to escape from the lungs, a thorough understanding of these processes can lay the foundation for new therapeutic approaches for bacterial pneumonia.
Topics: Animals; Bacteremia; Cross Infection; Humans; Lung; Pneumonia, Bacterial; Pseudomonas Infections; Pseudomonas aeruginosa; Type III Secretion Systems; Virulence; Virulence Factors
PubMed: 26407972
DOI: 10.1007/s00294-015-0522-x