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Toxins Apr 2020Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate... (Review)
Review
Bacterial toxins play a key role in the pathogenesis of lung disease. Based on their structural and functional properties, they employ various strategies to modulate lung barrier function and to impair host defense in order to promote infection. Although in general, these toxins target common cellular signaling pathways and host compartments, toxin- and cell-specific effects have also been reported. Toxins can affect resident pulmonary cells involved in alveolar fluid clearance (AFC) and barrier function through impairing vectorial Na transport and through cytoskeletal collapse, as such, destroying cell-cell adhesions. The resulting loss of alveolar-capillary barrier integrity and fluid clearance capacity will induce capillary leak and foster edema formation, which will in turn impair gas exchange and endanger the survival of the host. Toxins modulate or neutralize protective host cell mechanisms of both the innate and adaptive immunity response during chronic infection. In particular, toxins can either recruit or kill central players of the lung's innate immune responses to pathogenic attacks, i.e., alveolar macrophages (AMs) and neutrophils. Pulmonary disorders resulting from these toxin actions include, e.g., acute lung injury (ALI), the acute respiratory syndrome (ARDS), and severe pneumonia. When acute infection converts to persistence, i.e., colonization and chronic infection, lung diseases, such as bronchitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) can arise. The aim of this review is to discuss the impact of bacterial toxins in the lungs and the resulting outcomes for pathogenesis, their roles in promoting bacterial dissemination, and bacterial survival in disease progression.
Topics: Adaptive Immunity; Animals; Bacteria; Bacterial Infections; Bacterial Toxins; Disease Progression; Host-Pathogen Interactions; Humans; Immunity, Innate; Lung; Respiratory Tract Infections; Signal Transduction
PubMed: 32252376
DOI: 10.3390/toxins12040223 -
The Journal of Infection Jul 2016Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains... (Review)
Review
Patients with cystic fibrosis (CF) suffer from chronic lung infection and airway inflammation. Respiratory failure secondary to chronic or recurrent infection remains the commonest cause of death and accounts for over 90% of mortality. Bacteria as Staphylococcus aureus, Pseudomonas aeruginosa and Burkholderia cepacia complex have been regarded the main CF pathogens and their role in progressive lung decline has been studied extensively. Little attention has been paid to the role of Aspergillus spp. and other filamentous fungi in the pathogenesis of non-ABPA (allergic bronchopulmonary aspergillosis) respiratory disease in CF, despite their frequent recovery in respiratory samples. It has become more apparent however, that Aspergillus spp. may play an important role in chronic lung disease in CF. Research delineating the underlying mechanisms of Aspergillus persistence and infection in the CF lung and its link to lung deterioration is lacking. This review summarizes the Aspergillus disease phenotypes observed in CF, discusses the role of CFTR (cystic fibrosis transmembrane conductance regulator)-protein in innate immune responses and new treatment modalities.
Topics: Aspergillosis, Allergic Bronchopulmonary; Aspergillus fumigatus; Chronic Disease; Cystic Fibrosis; Cystic Fibrosis Transmembrane Conductance Regulator; Humans; Immunity, Innate; Lung; Phenotype; Pulmonary Aspergillosis
PubMed: 27177733
DOI: 10.1016/j.jinf.2016.04.022 -
Respiratory Research Dec 2020Pulmonary infections are associated with a brisk inflammatory reaction to bacterial surface components. Lipopolysaccharides (LPS) trigger macrophage activation and... (Review)
Review
Pulmonary infections are associated with a brisk inflammatory reaction to bacterial surface components. Lipopolysaccharides (LPS) trigger macrophage activation and release of mitochondrial metabolites that control the intensity of the immune response. Whereas succinate induces oxidative stress (ROS), HIF1α stabilization, glycolysis and IL-1β release, itaconate suppresses inflammation by inhibiting succinate oxidation, glycolytic flux and promoting anti-oxidant Nrf2-HO-1 functions. P. aeruginosa is a major pathogen associated with acute and chronic lung infection. Although both secreted toxins, LPS and proteases are key factors to establish acute P. aeruginosa pneumonia, lack of these components in chronic P. aeruginosa isolates suggest these organisms exploit other mechanisms to adapt and persist in the lung. Upon inhalation, P. aeruginosa strains trigger airway macrophage reprograming and bacterial variants obtained from acutely and chronically infected subjects exhibit metabolic adaptation consistent with succinate and itaconate assimilation; namely, high expression of extracellular polysaccharides (EPS), reduced lptD-LPS function, increased glyoxylate shunt (GS) activity and substantial biofilm production. In this review we discuss recent findings illustrating how P. aeruginosa induces and adapts to macrophage metabolites in the human lung, and that catabolism of succinate and itaconate contribute to their formidable abilities to tolerate oxidative stress, phagocytosis and immune clearance.
Topics: Animals; Biofilms; Energy Metabolism; Host-Pathogen Interactions; Humans; Inflammation Mediators; Lung; Macrophage Activation; Macrophages, Alveolar; Oxidative Stress; Pneumonia, Bacterial; Pseudomonas Infections; Pseudomonas aeruginosa; Reactive Oxygen Species
PubMed: 33302964
DOI: 10.1186/s12931-020-01591-x -
Current Opinion in Infectious Diseases Apr 2022Although nontuberculous mycobacterial pulmonary disease is increasing in incidence, outcomes remain less than optimal highlighting the unmet need for developing novel... (Review)
Review
PURPOSE OF REVIEW
Although nontuberculous mycobacterial pulmonary disease is increasing in incidence, outcomes remain less than optimal highlighting the unmet need for developing novel therapies.
RECENT FINDINGS
Several new antibiotic formulations, novel antibiotics, and novel nonantibiotic treatments have recently demonstrated positive results in treating nontuberculous mycobacterial pulmonary disease.
SUMMARY
Promising novel therapies are currently under investigation fueling much needed interest and enthusiasm in the nontuberculous mycobacterial pulmonary disease space and will hopefully lead to improved understanding and outcomes in this complex disease.
Topics: Anti-Bacterial Agents; Humans; Lung; Lung Diseases; Mycobacterium Infections, Nontuberculous; Opportunistic Infections
PubMed: 34966084
DOI: 10.1097/QCO.0000000000000815 -
Current Cardiology Reviews 2021In December 2019, a novel COVID-19 infection caused by SARS-CoV-2 has emerged as a global emergency. In a few months, the pathogen has infected millions of people in the... (Review)
Review
In December 2019, a novel COVID-19 infection caused by SARS-CoV-2 has emerged as a global emergency. In a few months, the pathogen has infected millions of people in the world. Primarily SARS-CoV-2 infects the pulmonary system which ultimately leads to ARDS and lung failure. The majority of patients develop milder symptoms but the infection turns severe in a huge number of people, which ultimately results in enhanced mortality in COVID-19 patients. Co-morbid conditions, primarily cardiovascular complications and diabetes, have been reported to show a strong correlation with COVID-19 severity. Further, the onset of myocardial injury secondary to pulmonary damage has been observed in critically ill patients who have never reported heart-related ailments before. Due to drastic health risks associated with virus infection, the unprecedented disruption in normal business throughout the world has caused economic misery. Apparently, newer treatments are urgently needed to combat the virus particularly to reduce the severity burden. Therefore, understanding the crosstalk between lung and heart during COVID-19 might give us better clarity for early diagnosis followed by appropriate treatment in patients with the likelihood of developing severe symptoms. Accordingly, the present review highlights the potential mechanisms that may explain the crosstalk between lung and heart so that effective treatment/management strategies can be evolved swiftly in this direction.
Topics: COVID-19; Heart; Heart Diseases; Humans; Lung; SARS-CoV-2
PubMed: 33305712
DOI: 10.2174/1573403X16999201210200614 -
Trends in Microbiology Aug 2017Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both... (Review)
Review
Lungs are directly exposed to the air, have enormous surface area, and enable gas exchange in air-breathing animals. They are constantly 'attacked' by microbes from both outside and inside and thus possess a unique, highly regulated local immune defense system which efficiently allows for microbial clearance while minimizing damaging inflammatory responses. As a prototypic host-adapted airborne pathogen, Mycobacterium tuberculosis traverses the lung and has several 'interaction points' (IPs) which it must overcome to cause infection. These interactions are critical, not only from a pathogenesis perspective but also in considering the effectiveness of therapies and vaccines in the lungs. Here we discuss emerging views on immunologic interactions occurring in the lungs for M. tuberculosis and their impact on infection and persistence.
Topics: Animals; Host-Pathogen Interactions; Humans; Immunity, Cellular; Immunity, Mucosal; Lung; Mice; Mycobacterium tuberculosis; Respiratory System; Tuberculosis, Pulmonary
PubMed: 28366292
DOI: 10.1016/j.tim.2017.03.007 -
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 -
Cell and Tissue Research Mar 2017Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by... (Review)
Review
Pneumonia is counted among the leading causes of death worldwide. Viruses, bacteria and pathogen-related molecules interact with cells present in the human alveolus by numerous, yet poorly understood ways. Traditional cell culture models little reflect the cellular composition, matrix complexity and three-dimensional architecture of the human lung. Integrative animal models suffer from species differences, which are of particular importance for the investigation of zoonotic lung diseases. The use of cultured ex vivo infected human lung tissue may overcome some of these limitations and complement traditional models. The present review gives an overview of common bacterial lung infections, such as pneumococcal infection and of widely neglected pathogens modeled in ex vivo infected lung tissue. The role of ex vivo infected lung tissue for the investigation of emerging viral zoonosis including influenza A virus and Middle East respiratory syndrome coronavirus is discussed. Finally, further directions for the elaboration of such models are revealed. Overall, the introduced models represent meaningful and robust methods to investigate principles of pathogen-host interaction in original human lung tissue.
Topics: Communicable Diseases; Humans; Lung; Lung Diseases; Models, Biological
PubMed: 27999962
DOI: 10.1007/s00441-016-2546-z -
Frontiers in Immunology 2021The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has... (Review)
Review
The majority of asthma exacerbations in children are caused by Rhinovirus (RV), a positive sense single stranded RNA virus of the Picornavirus family. The host has developed virus defense mechanisms that are mediated by the upregulation of interferon-activated signaling. However, the virus evades the immune system by inducing immunosuppressive cytokines and surface molecules like programmed cell death protein 1 (PD-1) and its ligand (PD-L1) on immunocompetent cells. Initially, RV infects epithelial cells, which constitute a physiologic mucosal barrier. Upon virus entrance, the host cell immediately recognizes viral components like dsRNA, ssRNA, viral glycoproteins or CpG-DNA by host pattern recognition receptors (PRRs). Activation of toll like receptors (TLR) 3, 7 and 8 within the endosome and through MDA-5 and RIG-I in the cytosol leads to the production of interferon (IFN) type I and other antiviral agents. Every cell type expresses IFNAR1/IFNAR2 receptors thus allowing a generalized antiviral activity of IFN type I resulting in the inhibition of viral replication in infected cells and preventing viral spread to non-infected cells. Among immune evasion mechanisms of the virus, there is downregulation of IFN type I and its receptor as well as induction of the immunosuppressive cytokine TGF-β. TGF-β promotes viral replication and is associated with induction of the immunosuppression signature markers LAP3, IDO and PD-L1. This article reviews the recent advances on the regulation of interferon type I expression in association with RV infection in asthmatics and the immunosuppression induced by the virus.
Topics: Adaptive Immunity; Animals; Asthma; Common Cold; Cytokines; Disease Progression; Host-Pathogen Interactions; Humans; Immune Evasion; Immunity, Innate; Immunocompromised Host; Lung; Rhinovirus; Signal Transduction
PubMed: 34691038
DOI: 10.3389/fimmu.2021.731846 -
Diagnostic Cytopathology Dec 2017Nocardia species and Actinomyces species are 2 of the most commonly diagnosed filamentous bacteria in routine cytopathology practice. These genera share many overlapping... (Review)
Review
Nocardia species and Actinomyces species are 2 of the most commonly diagnosed filamentous bacteria in routine cytopathology practice. These genera share many overlapping cytomorphologic features, including their thin, beaded, branching, Gram-positive, GMS-positive filamentous structures that fragment at their peripheries into bacillary- and coccoid-appearing forms. Features that help distinguish between these 2 microorganisms include the width of their filamentous structures, the angles at which they branch, and their ability or lack thereof to retain a modified acid-fast stain. In addition to cytomorphologic overlap, overlap in clinical presentation is frequent with pulmonary and mucocutaneous presentations seen in both. Differentiating between Nocardia and Actinomyces is essential because patients with these infections require different approaches to medical management. Both antibiotic susceptibilities and the need for early surgical intervention as part of the treatment plan vary greatly among these 2 groups. This review focuses on the clinical presentation, cytomorphology and staining characteristics that can be useful in identifying and distinguishing between Nocardia and Actinomyces infections, as well as their mimickers.
Topics: Actinomyces; Actinomycosis; Diagnosis, Differential; Humans; Lung; Nocardia; Nocardia Infections
PubMed: 28888064
DOI: 10.1002/dc.23816