Host-pathogen interplay in the respiratory environment of cystic fibrosis

Yonker, Lael M.; Cigana, Cristina; Hurley, Bryan P.; Bragonzi, Alessandra

doi:10.1016/j.jcf.2015.02.008

Cited by 62 publications

(64 citation statements)

References 106 publications

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“…This special interest in SCV occurrence and prevalence in CF is due to some special characteristics of CF airways, which are explained briefly in the following paragraph. For a deeper understanding, the reader is referred to recent reviews (64)(65)(66)(67)(68).…”

Section: Cystic Fibrosis Airway Infectionmentioning

confidence: 99%

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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SUMMARYSmall colony variants (SCVs) were first described more than 100 years ago forStaphylococcus aureusand various coagulase-negative staphylococci. Two decades ago, an association between chronic staphylococcal infections and the presence of SCVs was observed. Since then, many clinical studies and observations have been published which tie recurrent, persistent staphylococcal infections, including device-associated infections, bone and tissue infections, and airway infections of cystic fibrosis patients, to this special phenotype. By their intracellular lifestyle, SCVs exhibit so-called phenotypic (or functional) resistance beyond the classical resistance mechanisms, and they can often be retrieved from therapy-refractory courses of infection. In this review, the various clinical infections where SCVs can be expected and isolated, diagnostic procedures for optimized species confirmation, and the pathogenesis of SCVs, including defined underlying molecular mechanisms and the phenotype switch phenomenon, are presented. Moreover, relevant animal models and suggested treatment regimens, as well as the requirements for future research areas, are highlighted.

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Section: Cystic Fibrosis Airway Infectionmentioning

confidence: 99%

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

2016

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“…Host-pathogen interactions that are critically important in defining the resolution or persistence of inflammation in cystic fibrosis are discussed in the accompanying review by Yonker et al, [38]. Several other immune pathways have been reported to be dysregulated in individuals with CF.…”

Section: Other Dysregulated Immune Pathwaysmentioning

confidence: 99%

Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy

Cantin

Hartl

Konstan

et al. 2015

Journal of Cystic Fibrosis

386

322

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Lung disease is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). Although CF lung disease is primarily an infectious disorder, the associated inflammation is both intense and ineffective at clearing pathogens. Persistent high-intensity inflammation leads to permanent structural damage of the CF airways and impaired lung function that eventually results in respiratory failure and death. Several defective inflammatory responses have been linked to cystic fibrosis transmembrane conductance regulator (CFTR) deficiency including innate and acquired immunity dysregulation, cell membrane lipid abnormalities, various transcription factor signaling defects, as well as altered kinase and toll-like receptor responses. The inflammation of the CF lung is dominated by neutrophils that release oxidants and proteases, particularly elastase. Neutrophil elastase in the CF airway secretions precedes the appearance of bronchiectasis, and correlates with lung function deterioration and respiratory exacerbations. Anti-inflammatory therapies are therefore of particular interest for CF lung disease but must be carefully studied to avoid suppressing critical elements of the inflammatory response and thus worsening infection. This review examines the role of inflammation in the pathogenesis of CF lung disease, summarizes the results of past clinical trials and explores promising new anti-inflammatory options.

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“…Chronic infection and aberrant inflammation are hallmarks of CF (Yonker et al , 2015). Persistent infection with Pseudomonas aeruginosa , a typical pathogen in the CF airway, contributes to overzealous inflammation marked by pathological neutrophilic breach of the airway mucosa.…”

Section: Introductionmentioning

confidence: 99%

Expansion of Airway Basal Cells and Generation of Polarized Epithelium

et al. 2018

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Airway basal stem cells are the progenitor cells within the airway that exhibit the capacity to self-renew and give rise to multiple types of differentiated airway epithelial cells. This stem cell-derived epithelium displays organized architecture with functional attributes of the airway mucosa. A protocol has been developed to culture and expand human airway basal stem cells while preserving their stem cell properties and capacity for subsequent mucociliary differentiation. This achievement presents a previously unrealized opportunity to maintain a durable supply of progenitor cells derived from healthy donors to differentiate into human primary airway epithelium for cellular and molecular-based studies. Further, basal stem cells can be harvested from patients with a specific airway disease, such as cystic fibrosis, enabling investigation of potentially altered behavior of disease-specific cells in the appropriate context of the airway mucosa. Here we describe, in detail, a protocol for the serial expansion of airway basal stem cells to enable the generation of nearly unlimited airway basal cells that can be stored and readily available for subsequent culturing and differentiation. In addition, we describe culturing and differentiation of airway basal stem cells on permeable transwell filters at air-liquid interface to create functional mucociliary pseudostratified polarized airway epithelial mucosa.

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Host-pathogen interplay in the respiratory environment of cystic fibrosis

Cited by 62 publications

References 106 publications

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

Clinical Significance and Pathogenesis of Staphylococcal Small Colony Variants in Persistent Infections

Inflammation in cystic fibrosis lung disease: Pathogenesis and therapy

Expansion of Airway Basal Cells and Generation of Polarized Epithelium

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