Update on host-pathogen interactions in cystic fibrosis lung disease

Hector, Andreas; Frey, Nina; Hartl, Dominik

doi:10.1186/s40348-016-0039-5

Cited by 14 publications

(8 citation statements)

References 39 publications

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“…However, a detailed study of day-to-day stability of the microbiome indicated that although the CF airway microbiota is relatively stable during periods of clinical stability, structural changes do occur which are associated with some, but not all, pulmonary exacerbations [152]. In other cases, an active subgroup of the lung microbiota may cause subtle changes in the microbiota which drive the onset of exacerbations [153]. It is possible that lung environmental alterations such as sub-inhibitory concentrations of antibiotics and host immune factors could cause changes in the virulence factors in the pathogens or changes in the functionality or metabolic activities of the microbiome, triggering exacerbations (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, the amount of neutrophil elastase overcomes the blocking anti-proteinases in CF [165] which can harm pulmonary matrix. Because NE levels correspond positively to neutrophil counts, and IL-8, IL-1ß and matrix metalloproteinase-9 levels, they are considered a significant marker for predicting CF infection and diseases [153, 166]. In addition, studies have shown that neutrophil elastase is capable of degrading CFTR [165] as well as cell surface receptors such as CD2, CD4, CD8, complement receptor 1 and antigen presentation receptors.…”

Section: Discussionmentioning

confidence: 99%

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Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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BackgroundThe airways of patients with cystic fibrosis (CF) are highly complex, subject to various environmental conditions as well as a distinct microbiota. Pseudomonas aeruginosa is recognized as one of the most important pulmonary pathogens and the predominant cause of morbidity and mortality in CF. A multifarious interplay between the host, pathogens, microbiota, and the environment shapes the course of the disease. There have been several excellent reviews detailing CF pathology, Pseudomonas and the role of environment in CF but only a few reviews connect these entities with regards to influence on the overall course of the disease. A holistic understanding of contributing factors is pertinent to inform new research and therapeutics.DiscussionIn this article, we discuss the deterministic alterations in lung physiology as a result of CF. We also revisit the impact of those changes on the microbiota, with special emphasis on P. aeruginosa and the influence of other non-genetic factors on CF. Substantial past and current research on various genetic and non-genetic aspects of cystic fibrosis has been reviewed to assess the effect of different factors on CF pulmonary infection. A thorough review of contributing factors in CF and the alterations in lung physiology indicate that CF lung infection is multi-factorial with no isolated cause that should be solely targeted to control disease progression. A combinatorial approach may be required to ensure better disease outcomes.ConclusionCF lung infection is a complex disease and requires a broad multidisciplinary approach to improve CF disease outcomes. A holistic understanding of the underlying mechanisms and non-genetic contributing factors in CF is central to development of new and targeted therapeutic strategies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

et al. 2016

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“…Recombinant purified forms of OmpA has been shown to activate both macrophages (Soulas et al 2000 ), dendritic cells (DCs) (Jeannin et al 2000 ; Lee et al 2010 ) and neutrophils (Mantovani et al 2011 ) in a receptor-dependent manner, suggesting that OmpA functions as a molecular pattern that activates the immune system. In CF lung disease, neutrophils are the most rapid and predominant innate immune cell type to transmigrate into the infected CF airway compartment (Hector et al 2016 ). Previously, we observed colocalization of Bcc and neutrophils by immunofluorescence staining of Bcc infected CF lung tissue samples who underwent transplantation, suggesting Bcc persistence within neutrophils in CF patients (Sousa et al 2007 ).…”

Section: Discussionmentioning

confidence: 99%

The Burkholderia cenocepacia OmpA-like protein BCAL2958: identification, characterization, and detection of anti-BCAL2958 antibodies in serum from B. cepacia complex-infected Cystic Fibrosis patients

et al. 2016

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Respiratory infections by bacteria of the Burkholderia cepacia complex (Bcc) remain an important cause of morbidity and mortality among cystic fibrosis patients, highlighting the need for novel therapeutic strategies. In the present work we have studied the B. cenocepacia protein BCAL2958, a member of the OmpA-like family of proteins, demonstrated as highly immunogenic in other pathogens and capable of eliciting strong host immune responses. The encoding gene was cloned and the protein, produced as a 6× His-tagged derivative, was used to produce polyclonal antibodies. Bioinformatics analyses led to the identification of sequences encoding proteins with a similarity higher than 96 % to BCAL2958 in all the publicly available Bcc genomes. Furthermore, using the antibody it was experimentally demonstrated that this protein is produced by all the 12 analyzed strains from 7 Bcc species. In addition, results are also presented showing the presence of anti-BCAL2958 antibodies in sera from cystic fibrosis patients with a clinical record of respiratory infection by Bcc, and the ability of the purified protein to in vitro stimulate neutrophils. The widespread production of the protein by Bcc members, together with its ability to stimulate the immune system and the detection of circulating antibodies in patients with a documented record of Bcc infection strongly suggest that the protein is a potential candidate for usage in preventive therapies of infections by Bcc.

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“…In young patients, primarily S. aureus and H. influenzae colonize in the airways. P. aeruginosa dominates at later stages, although other bacterial species also have been seen to form biofilm in the lungs of CF patients [189].…”

Section: Cystic Fibrosis (Cf)mentioning

confidence: 99%

Bacterial Biofilm and its Role in the Pathogenesis of Disease

et al. 2020

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Recognition of the fact that bacterial biofilm may play a role in the pathogenesis of disease has led to an increased focus on identifying diseases that may be biofilm-related. Biofilm infections are typically chronic in nature, as biofilm-residing bacteria can be resilient to both the immune system, antibiotics, and other treatments. This is a comprehensive review describing biofilm diseases in the auditory, the cardiovascular, the digestive, the integumentary, the reproductive, the respiratory, and the urinary system. In most cases reviewed, the biofilms were identified through various imaging technics, in addition to other study approaches. The current knowledge on how biofilm may contribute to the pathogenesis of disease indicates a number of different mechanisms. This spans from biofilm being a mere reservoir of pathogenic bacteria, to playing a more active role, e.g., by contributing to inflammation. Observations also indicate that biofilm does not exclusively occur extracellularly, but may also be formed inside living cells. Furthermore, the presence of biofilm may contribute to development of cancer. In conclusion, this review shows that biofilm is part of many, probably most chronic infections. This is important knowledge for development of effective treatment strategies for such infections.

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Update on host-pathogen interactions in cystic fibrosis lung disease

Cited by 14 publications

References 39 publications

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

Cystic fibrosis lung environment and Pseudomonas aeruginosa infection

The Burkholderia cenocepacia OmpA-like protein BCAL2958: identification, characterization, and detection of anti-BCAL2958 antibodies in serum from B. cepacia complex-infected Cystic Fibrosis patients

Bacterial Biofilm and its Role in the Pathogenesis of Disease

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