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Clinical Microbiology and Infection :... Mar 2019Rhodococcus equi is a recognized cause of disease in humans, especially in individuals who are immunocompromised. Because diphtheroids are regarded as part of normal... (Review)
Review
BACKGROUND
Rhodococcus equi is a recognized cause of disease in humans, especially in individuals who are immunocompromised. Because diphtheroids are regarded as part of normal respiratory flora, the importance of R. equi as a pulmonary pathogen may not be fully appreciated and its prevalence may be underestimated. Most treatment recommendations for R. equi infection were established before antiretroviral drugs became available for human immunodeficiency virus/AIDS therapy, and therapeutic strategies may need to be updated.
OBJECTIVES
To review the role of R. equi as a cause of pulmonary infection; to highlight its importance for clinicians and microbiologists; and to challenge current approaches to treatment, whether in immunodeficient or immunocompetent individuals.
SOURCES
A PubMed search using combinations of the following terms: 'Rhodococcus (automatically including Corynebacterium) equi' AND 'pneumonia' OR 'pulmonary' infection, then cross-checking references in the resulting cases, case series and reviews.
CONTENT
We provide a review that details the challenges in the diagnosis, microbiology and pathogenesis of pulmonary infection caused by R. equi and the options for treatment.
IMPLICATIONS
Ten to 14 days of treatment may be effective for pneumonia due to R. equi. Our review suggests that longer courses of therapy are needed for cavitary lesions and lung masses. However, recommendations for excessively prolonged treatment of all pulmonary infections arose during a time when many cases occurred in individuals with AIDS and before effective antiretroviral therapy was available. We suggest that the rationale for prolonged therapy with multiple antibiotics needs to be re-evaluated.
Topics: AIDS-Related Opportunistic Infections; Actinomycetales Infections; Anti-Bacterial Agents; Disease Management; Humans; Immunocompromised Host; Lung; Pneumonia, Bacterial; Rhodococcus equi
PubMed: 29777923
DOI: 10.1016/j.cmi.2018.04.033 -
Nature Jan 2015Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and...
Lung diseases such as chronic obstructive pulmonary disease and pulmonary fibrosis involve the progressive and inexorable destruction of oxygen exchange surfaces and airways, and have emerged as a leading cause of death worldwide. Mitigating therapies, aside from impractical organ transplantation, remain limited and the possibility of regenerative medicine has lacked empirical support. However, it is clinically known that patients who survive sudden, massive loss of lung tissue from necrotizing pneumonia or acute respiratory distress syndrome often recover full pulmonary function within six months. Correspondingly, we recently demonstrated lung regeneration in mice following H1N1 influenza virus infection, and linked distal airway stem cells expressing Trp63 (p63) and keratin 5, called DASC(p63/Krt5), to this process. Here we show that pre-existing, intrinsically committed DASC(p63/Krt5) undergo a proliferative expansion in response to influenza-induced lung damage, and assemble into nascent alveoli at sites of interstitial lung inflammation. We also show that the selective ablation of DASC(p63/Krt5) in vivo prevents this regeneration, leading to pre-fibrotic lesions and deficient oxygen exchange. Finally, we demonstrate that single DASC(p63/Krt5)-derived pedigrees differentiate to type I and type II pneumocytes as well as bronchiolar secretory cells following transplantation to infected lung and also minimize the structural consequences of endogenous stem cell loss on this process. The ability to propagate these cells in culture while maintaining their intrinsic lineage commitment suggests their potential in stem cell-based therapies for acute and chronic lung diseases.
Topics: Animals; Bronchioles; Cell Differentiation; Cell Lineage; Cell Proliferation; Dogs; Humans; Influenza A Virus, H1N1 Subtype; Keratin-5; Lung; Madin Darby Canine Kidney Cells; Mice; Orthomyxoviridae Infections; Oxygen; Pedigree; Phosphoproteins; Pneumonia; Pulmonary Alveoli; Re-Epithelialization; Regeneration; Stem Cell Transplantation; Stem Cells; Trans-Activators
PubMed: 25383540
DOI: 10.1038/nature13903 -
Frontiers in Immunology 2021Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical... (Review)
Review
Schistosome infection is a major cause of global morbidity, particularly in sub-Saharan Africa. However, there is no effective vaccine for this major neglected tropical disease, and re-infection routinely occurs after chemotherapeutic treatment. Following invasion through the skin, larval schistosomula enter the circulatory system and migrate through the lung before maturing to adulthood in the mesenteric or urogenital vasculature. Eggs released from adult worms can become trapped in various tissues, with resultant inflammatory responses leading to hepato-splenic, intestinal, or urogenital disease - processes that have been extensively studied in recent years. In contrast, although lung pathology can occur in both the acute and chronic phases of schistosomiasis, the mechanisms underlying pulmonary disease are particularly poorly understood. In chronic infection, egg-mediated fibrosis and vascular destruction can lead to the formation of portosystemic shunts through which eggs can embolise to the lungs, where they can trigger granulomatous disease. Acute schistosomiasis, or Katayama syndrome, which is primarily evident in non-endemic individuals, occurs during pulmonary larval migration, maturation, and initial egg-production, often involving fever and a cough with an accompanying immune cell infiltrate into the lung. Importantly, lung migrating larvae are not just a cause of inflammation and pathology but are a key target for future vaccine design. However, vaccine efforts are hindered by a limited understanding of what constitutes a protective immune response to larvae. In this review, we explore the current understanding of pulmonary immune responses and inflammatory pathology in schistosomiasis, highlighting important unanswered questions and areas for future research.
Topics: Animals; Disease Models, Animal; Host-Parasite Interactions; Humans; Immune Evasion; Lung; Lung Diseases, Parasitic; Mice; Protozoan Vaccines; Schistosoma; Schistosomiasis; Schistosomicides
PubMed: 33953712
DOI: 10.3389/fimmu.2021.635513 -
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 -
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 -
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 -
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 -
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 -
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 -
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