scholarly journals A Review of The Role of The Microbiome on Immune Responses and Its Association With Cystic Fibrosis

2021 ◽  
Vol 3 (2) ◽  
pp. 75-88
Author(s):  
Mahtab Ghorban Movahed ◽  
◽  
Ahya Abdi Ali ◽  
Keyword(s):  
Cystic Fibrosis ◽  
Immune Responses ◽  
Lung Diseases ◽  
Complex Disease ◽  
Pulmonary Complications ◽  
Host Susceptibility ◽  
Chronic Obstructive ◽  
Chronic Lung Diseases ◽  
The Impact

In recent years, the microbiome has been recognized as a key regulator of immune responses. Evidence suggests that changes in the microbiome can lead to chronic disease and even exacerbation of the disease. Impairment of innate immunity resulting from microbial incompatibility may worsen host susceptibility to infection and exacerbate chronic lung diseases. Specific microbes play a key role in improving immune responses and microbial incompatibility is involved in chronic lung diseases such as asthma, chronic obstructive pulmonary disease, and Cystic Fibrosis (CF). CF is an extremely complex disease that results from a gene mutation. Lack of expression of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) has late complications. Incompatibility in lung microbiota is associated with chronic lung diseases, but it is not determined whether this incompatibility can cause health problems or ineffective regulation of immune response create the disease and its progression. In the CF, due to the deficiency of the immune system, many opportunistic microorganisms, including Pseudomonas. aeruginosa or Staphylococcus aureus are colonized in the patient’s lung and due to an immunodeficiency causedby a defect in the system CFTR, lungs are unable to clear the bacteria that leads to severe pulmonary complications and respiratory and digestive problems in such patients. Therefore, in these patients, the microbiome contributes to dysfunctional immune responses and disease exacerbations. This review summarizes the impact of the microbiome on host immune responses and its relationship with CF to explore the role of the microbiome in causing CF.

scholarly journals Does cystic fibrosis constitute an advantage in COVID-19 infection?

2020 ◽  
Vol 46 (1) ◽  
Author(s):  
Valentino Bezzerri ◽  
Francesca Lucca ◽  
Sonia Volpi ◽  
Marco Cipolli
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Diseases ◽  
Respiratory Viruses ◽  
Chronic Obstructive ◽  
Veneto Region ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Italian Regions ◽  
Pulmonary Impairment

Abstract The Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.

scholarly journals Influence of Hypoxia on the Epithelial-Pathogen Interactions in the Lung: Implications for Respiratory Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Lee K. Page ◽  
Karl J. Staples ◽  
C. Mirella Spalluto ◽  
Alastair Watson ◽  
Tom M. A. Wilkinson
Keyword(s):  
Airway Epithelium ◽  
Lung Diseases ◽  
Respiratory Diseases ◽  
Molecular Mechanisms ◽  
Complex Disease ◽  
Tissue Hypoxia ◽  
Current Evidence ◽  
Chronic Obstructive ◽  
Respiratory Pathogens

Under normal physiological conditions, the lung remains an oxygen rich environment. However, prominent regions of hypoxia are a common feature of infected and inflamed tissues and many chronic inflammatory respiratory diseases are associated with mucosal and systemic hypoxia. The airway epithelium represents a key interface with the external environment and is the first line of defense against potentially harmful agents including respiratory pathogens. The protective arsenal of the airway epithelium is provided in the form of physical barriers, and the production of an array of antimicrobial host defense molecules, proinflammatory cytokines and chemokines, in response to activation by receptors. Dysregulation of the airway epithelial innate immune response is associated with a compromised immunity and chronic inflammation of the lung. An increasing body of evidence indicates a distinct role for hypoxia in the dysfunction of the airway epithelium and in the responses of both innate immunity and of respiratory pathogens. Here we review the current evidence around the role of tissue hypoxia in modulating the host-pathogen interaction at the airway epithelium. Furthermore, we highlight the work needed to delineate the role of tissue hypoxia in the pathophysiology of chronic inflammatory lung diseases such as asthma, cystic fibrosis, and chronic obstructive pulmonary disease in addition to novel respiratory diseases such as COVID-19. Elucidating the molecular mechanisms underlying the epithelial-pathogen interactions in the setting of hypoxia will enable better understanding of persistent infections and complex disease processes in chronic inflammatory lung diseases and may aid the identification of novel therapeutic targets and strategies.

scholarly journals Role of the Microbiome in Interstitial Lung Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Ozioma S. Chioma ◽  
Laura E. Hesse ◽  
Austin Chapman ◽  
Wonder P. Drake
Keyword(s):  
Immune Responses ◽  
Lung Disease ◽  
Microbial Communities ◽  
Lung Diseases ◽  
Interstitial Lung Diseases ◽  
Original Research ◽  
Inflammatory Conditions ◽  
Lung Health ◽  
The Impact

There are trillions of microorganisms in the human body, consisting of bacteria, viruses, fungi, and archaea; these collectively make up the microbiome. Recent studies suggest that the microbiome may serve as a biomarker for disease, a therapeutic target, or provide an explanation for pathophysiology in lung diseases. Studies describing the impact of the microorganisms found in the respiratory tract on lung health have been published and are discussed here in the context of interstitial lung diseases. Additionally, epidemiological and experimental evidence highlights the importance of cross-talk between the gut microbiota and the lungs, called the gut–lung axis. The gut-lung axis postulates that alterations in gut microbial communities may have a profound effect on lung disease. Dysbiosis in the microbial community of the gut is linked with changes in immune responses, homeostasis in the airways, and inflammatory conditions in the gastrointestinal tract itself. In this review, we summarize studies describing the role of the microbiome in interstitial lung disease and discuss the implications of these findings on the diagnosis and treatment of these diseases. This paper describes the impact of the microbial communities on the pathogenesis of lung diseases by assessing recent original research and identifying remaining gaps in knowledge.

scholarly journals Proteases, Mucus, and Mucosal Immunity in Chronic Lung Disease

2021 ◽  
Vol 22 (9) ◽  
pp. 5018
Author(s):  
Michael C. McKelvey ◽  
Ryan Brown ◽  
Sinéad Ryan ◽  
Marcus A. Mall ◽  
Sinéad Weldon ◽  
...  
Keyword(s):  
Cystic Fibrosis ◽  
Lung Disease ◽  
Lung Diseases ◽  
Lung Damage ◽  
Chronic Obstructive ◽  
Lung Function Decline ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Multifunctional Enzymes ◽  
Disease Experience

Dysregulated protease activity has long been implicated in the pathogenesis of chronic lung diseases and especially in conditions that display mucus obstruction, such as chronic obstructive pulmonary disease, cystic fibrosis, and non-cystic fibrosis bronchiectasis. However, our appreciation of the roles of proteases in various aspects of such diseases continues to grow. Patients with muco-obstructive lung disease experience progressive spirals of inflammation, mucostasis, airway infection and lung function decline. Some therapies exist for the treatment of these symptoms, but they are unable to halt disease progression and patients may benefit from novel adjunct therapies. In this review, we highlight how proteases act as multifunctional enzymes that are vital for normal airway homeostasis but, when their activity becomes immoderate, also directly contribute to airway dysfunction, and impair the processes that could resolve disease. We focus on how proteases regulate the state of mucus at the airway surface, impair mucociliary clearance and ultimately, promote mucostasis. We discuss how, in parallel, proteases are able to promote an inflammatory environment in the airways by mediating proinflammatory signalling, compromising host defence mechanisms and perpetuating their own proteolytic activity causing structural lung damage. Finally, we discuss some possible reasons for the clinical inefficacy of protease inhibitors to date and propose that, especially in a combination therapy approach, proteases represent attractive therapeutic targets for muco-obstructive lung diseases.

scholarly journals Role of Apoptosis in Amplifying Inflammatory Responses in Lung Diseases

2010 ◽  
Vol 3 ◽  
pp. JCD.S5375 ◽  
Author(s):  
E.P. Schmidt ◽  
R.M. Tuder
Keyword(s):  
Lung Diseases ◽  
Inflammatory Responses ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Disease States ◽  
Chronic Lung Diseases ◽  
Cellular Environment ◽  
Molecular Patterns ◽  
Dying Cells

Apoptosis is an important contributor to the pathophysiology of lung diseases such as acute lung injury (ALI) and chronic obstructive pulmonary disease (COPD). Furthermore, the cellular environment of these acute and chronic lung diseases favors the delayed clearance of apoptotic cells. This dysfunctional efferocytosis predisposes to the release of endogenous ligands from dying cells. These so-called damage-associated molecular patterns (DAMPs) play an important role in the stimulation of innate immunity as well as in the induction of adaptive immunity, potentially against autoantigens. In this review, we explore the role of apoptosis in ALI and COPD, with particular attention to the contribution of DAMP release in augmenting the inflammatory response in these disease states.

scholarly journals Redox Dysregulation in Aging and COPD: Role of NOX Enzymes and Implications for Antioxidant Strategies

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1799
Author(s):  
Caspar Schiffers ◽  
Niki L. Reynaert ◽  
Emiel F. M. Wouters ◽  
Albert van der Vliet
Keyword(s):  
Lung Disease ◽  
Lung Diseases ◽  
Chronic Obstructive ◽  
Obstructive Pulmonary Disease ◽  
Antioxidant Responses ◽  
Related Disease ◽  
Age Related ◽  
The Impact ◽  
Important Enzyme

With a rapidly growing elderly human population, the incidence of age-related lung diseases such as chronic obstructive pulmonary disease (COPD) continues to rise. It is widely believed that reactive oxygen species (ROS) play an important role in ageing and in age-related disease, and approaches of antioxidant supplementation have been touted as useful strategies to mitigate age-related disease progression, although success of such strategies has been very limited to date. Involvement of ROS in ageing is largely attributed to mitochondrial dysfunction and impaired adaptive antioxidant responses. NADPH oxidase (NOX) enzymes represent an important enzyme family that generates ROS in a regulated fashion for purposes of oxidative host defense and redox-based signalling, however, the associations of NOX enzymes with lung ageing or age-related lung disease have to date only been minimally addressed. The present review will focus on our current understanding of the impact of ageing on NOX biology and its consequences for age-related lung disease, particularly COPD, and will also discuss the implications of altered NOX biology for current and future antioxidant-based strategies aimed at treating these diseases.

scholarly journals Role of extracellular vesicles in chronic lung disease

Thorax ◽  
2021 ◽  
pp. thoraxjnl-2020-216370
Author(s):  
Anne Trappe ◽  
Seamas C Donnelly ◽  
Paul McNally ◽  
Judith A Coppinger
Keyword(s):  
Lung Disease ◽  
Extracellular Vesicles ◽  
Chronic Lung Disease ◽  
Lung Diseases ◽  
Drug Carriers ◽  
Chronic Obstructive ◽  
Sources Of Information ◽  
Chronic Obstructive Pulmonary Disorder ◽  
Chronic Lung Diseases

To explore the role of extracellular vesicles (EVs) in chronic lung diseases.EVs are emerging as mediators of intercellular communication and possible diagnostic markers of disease. EVs harbour cargo molecules including RNA, lipids and proteins that they transfer to recipient cells. EVs are intercellular communicators within the lung microenvironment. Due to their disease-specific cargoes, EVs have the promise to be all-in-one complex multimodal biomarkers. EVs also have potential as drug carriers in chronic lung disease.Descriptive discussion of key studies of EVs as contributors to disease pathology, as biomarkers and as potential therapies with a focus on chronic obstructive pulmonary disorder (COPD), cystic fibrosis (CF), asthma, idiopathic pulmonary fibrosis and lung cancer.We provide a broad overview of the roles of EV in chronic respiratory disease. Recent advances in profiling EVs have shown their potential as biomarker candidates. Further studies have provided insight into their disease pathology, particularly in inflammatory processes across a spectrum of lung diseases. EVs are on the horizon as new modes of drug delivery and as therapies themselves in cell-based therapeutics.EVs are relatively untapped sources of information in the clinic that can help further detail the full translational nature of chronic lung disorders.

scholarly journals Does Cystic Fibrosis Constitute an Advantage in COVID-19 Infection?

2020 ◽  
Author(s):  
Valentino Bezzerri ◽  
Francesca Lucca ◽  
Sonia Volpi ◽  
Marco Cipolli
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Cystic Fibrosis ◽  
Lung Diseases ◽  
Respiratory Viruses ◽  
Chronic Obstructive ◽  
Veneto Region ◽  
Obstructive Pulmonary Disease ◽  
Chronic Lung Diseases ◽  
Italian Regions ◽  
Pulmonary Impairment

Abstract The Veneto region is one of the most affected Italian regions by COVID-19. Chronic lung diseases, such as chronic obstructive pulmonary disease (COPD), may constitute a risk factor in COVID-19. Moreover, respiratory viruses were generally associated with severe pulmonary impairment in cystic fibrosis (CF). We would have therefore expected numerous cases of severe COVID-19 among the CF population. Surprisingly, we found that CF patients were significantly protected against infection by SARS-CoV-2. We discussed this aspect formulating some reasonable theories.

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