Neutrophils in cystic fibrosis

Laval, Julie; Ralhan, Anjali; Hartl, Dominik

doi:10.1515/hsz-2015-0271

Cited by 70 publications

(68 citation statements)

References 125 publications

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“…In particular, recent studies showed that upon recruitment into CF airways neutrophils undergo significant activation of both cAMP response element-binding protein (CREB) and mechanistic (formerly mammalian) target of rapamycin (mTOR) pathways, linked to surface upregulation of functional receptors (e.g., the receptor for advanced glycation end products) and metabolite transporters (e.g., glucose and amino acid transporters Glut1 and ASCT2) [43–45]. Since CF airways are enriched in inflammatory mediators and nutrients such as glucose and amino acids, these results suggest the ability of neutrophils to adapt to specific microenvironments through coordinated stress responses and metabolic reprogramming [reviewed in 46, 47]. …”

Section: Neutrophilsmentioning

confidence: 99%

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

et al. 2018

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The respiratory tract is faced daily with 10,000 L of inhaled air. While the majority of air contains harmless environmental components, the pulmonary immune system also has to cope with harmful microbial or sterile threats and react rapidly to protect the host at this intimate barrier zone. The airways are endowed with a broad armamentarium of cellular and humoral host defense mechanisms, most of which belong to the innate arm of the immune system. The complex interplay between resident and infiltrating immune cells and secreted innate immune proteins shapes the outcome of host-pathogen, host-allergen, and host-particle interactions within the mucosal airway compartment. Here, we summarize and discuss recent findings on pulmonary innate immunity and highlight key pathways relevant for biomarker and therapeutic targeting strategies for acute and chronic diseases of the respiratory tract.

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Section: Neutrophilsmentioning

confidence: 99%

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

et al. 2018

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“…Although exciting results are emerging with regard to the direct or indirect mechanisms by which CFTR affects PMN functions in CF, future research using novel tools like a PMN-specific conditional CFTR knockout mouse strain could help better answer this question. Several excellent reviews provide a deeper insight into this field [173,174,175]. …”

Section: Pmn Dysfunction In Cfmentioning

confidence: 99%

Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis

Rada

2017

Pathogens

102

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Cystic fibrosis (CF) affects 70,000 patients worldwide. Morbidity and mortality in CF is largely caused by lung complications due to the triad of impaired mucociliary clearance, microbial infections and chronic inflammation. Cystic fibrosis airway inflammation is mediated by robust infiltration of polymorphonuclear neutrophil granulocytes (PMNs, neutrophils). Neutrophils are not capable of clearing lung infections and contribute to tissue damage by releasing their dangerous cargo. Pseudomonas aeruginosa is an opportunistic pathogen causing infections in immunocompromised individuals. P. aeruginosa is a main respiratory pathogen in CF infecting most patients. Although PMNs are key to attack and clear P. aeruginosa in immunocompetent individuals, PMNs fail to do so in CF. Understanding why neutrophils cannot clear P. aeruginosa in CF is essential to design novel therapies. This review provides an overview of the antimicrobial mechanisms by which PMNs attack and eliminate P. aeruginosa. It also summarizes current advances in our understanding of why PMNs are incapable of clearing P. aeruginosa and how this bacterium adapts to and resists PMN-mediated killing in the airways of CF patients chronically infected with P. aeruginosa.

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“…Among those, neutrophil burden and extracellular activity of the protease neutrophil elastase (NE) in CF airway fluid correlate best with disease progression in CF patients, from infancy to adulthood [8]. The role of neutrophil inflammation in CF pathophysiology has been exhaustively reviewed elsewhere [9–11]. Recent reviews detail the putative role of other immune cells, such as macrophages, in CF lung disease [12–14].…”

Section: Introductionmentioning

confidence: 99%

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

Margaroli

Tirouvanziam

2016

Mol Cell Pediatr

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IntroductionThe pathological course of several chronic inflammatory diseases, including cystic fibrosis, chronic obstructive pulmonary disease, and rheumatoid arthritis, features an aberrant innate immune response dominated by neutrophils. In cystic fibrosis, neutrophil burden and activity of neutrophil elastase in the extracellular fluid have been identified as strong predictors of lung disease severity.ReviewAlthough neutrophils are generally considered to be rigid, pre-programmed effector leukocytes, recent studies suggest extensive plasticity in how neutrophil functions unfold upon recruitment to peripheral tissues, and how they choose their ultimate fate. Indeed, upon migration to cystic fibrosis airways, neutrophils display dysregulated lifespan, metabolic activation, and altered effector and regulatory functions, consistent with profound adaptation and phenotypic reprogramming. Licensed by signals present in cystic fibrosis airway microenvironment to survive and develop these novel functions, neutrophils orchestrate, in partnership with the epithelium and with the resident microbiota, the evolution of a pathological microenvironment. This microenvironment is defined by altered proteolytic, redox, and metabolic balance and the presence of stable luminal structures in which neutrophils and microbes coexist.ConclusionsThe elucidation of molecular mechanisms driving neutrophil plasticity in vivo will open new treatment opportunities designed to modulate, rather than block, the crucial adaptive functions fulfilled by neutrophils. This review aims to outline emerging mechanisms of neutrophil plasticity and their participation in the building of pathological microenvironments in the context of cystic fibrosis and other diseases with similar features.

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Neutrophils in cystic fibrosis

Cited by 70 publications

References 125 publications

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

Innate Immunity of the Lung: From Basic Mechanisms to Translational Medicine

Interactions between Neutrophils and Pseudomonas aeruginosa in Cystic Fibrosis

Neutrophil plasticity enables the development of pathological microenvironments: implications for cystic fibrosis airway disease

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