Advertisement

Topics

Cathelicidin is a "fire alarm", generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa.

08:00 EDT 12th April 2019 | BioPortfolio

Summary of "Cathelicidin is a "fire alarm", generating protective NLRP3-dependent airway epithelial cell inflammatory responses during infection with Pseudomonas aeruginosa."

Pulmonary infections are a major global cause of morbidity, exacerbated by an increasing threat from antibiotic-resistant pathogens. In this context, therapeutic interventions aimed at protectively modulating host responses, to enhance defence against infection, take on ever greater significance. Pseudomonas aeruginosa is an important multidrug-resistant, opportunistic respiratory pathogen, the clearance of which can be enhanced in vivo by the innate immune modulatory properties of antimicrobial host defence peptides from the cathelicidin family, including human LL-37. Initially described primarily as bactericidal agents, cathelicidins are now recognised as multifunctional antimicrobial immunomodulators, modifying host responses to pathogens, but the key mechanisms involved in these protective functions are not yet defined. We demonstrate that P. aeruginosa infection of airway epithelial cells promotes extensive infected cell internalisation of LL-37, in a manner that is dependent upon epithelial cell interaction with live bacteria, but does not require bacterial Type 3 Secretion System (T3SS). Internalised LL-37 acts as a second signal to induce inflammasome activation in airway epithelial cells, which, in contrast to myeloid cells, are relatively unresponsive to P. aeruginosa. We demonstrate that this is mechanistically dependent upon cathepsin B release, and NLRP3-dependent activation of caspase 1. These result in LL-37-mediated release of IL-1β and IL-18 in a manner that is synergistic with P. aeruginosa infection, and can induce caspase 1-dependent death of infected epithelial cells, and promote neutrophil chemotaxis. We propose that cathelicidin can therefore act as a second signal, required by P. aeruginosa infected epithelial cells to promote an inflammasome-mediated altruistic cell death of infection-compromised epithelial cells and act as a "fire alarm" to enhance rapid escalation of protective inflammatory responses to an uncontrolled infection. Understanding this novel modulatory role for cathelicidins, has the potential to inform development of novel therapeutic strategies to antibiotic-resistant pathogens, harnessing innate immunity as a complementation or alternative to current interventions.

Affiliation

Journal Details

This article was published in the following journal.

Name: PLoS pathogens
ISSN: 1553-7374
Pages: e1007694

Links

DeepDyve research library

PubMed Articles [9352 Associated PubMed Articles listed on BioPortfolio]

Lack of Protein Prenylation Promotes Nlrp3 Inflammasome Assembly in Human Monocytes.

We demonstrate that blocking the mevalonate pathway and protein prenylation in human monocytes leads to enhanced activity of an NLRP3-dependent, but not Pyrin-dependent, inflammasome, suggesting a pro...

The role of mitochondria in NLRP3 inflammasome activation.

The NLRP3 inflammasome is a multiprotein platform which is activated upon cellular infection or stress. Its activation leads to caspase-1-dependent secretion of proinflammatory cytokines like interleu...

Nobiletin alleviates palmitic acid‑induced NLRP3 inflammasome activation in a sirtuin 1‑dependent manner in AML‑12 cells.

The NOD‑like receptor family pyrin domain containing 3 (NLRP3) inflammasome has been reported to contribute to palmitic acid (PA)‑induced lipotoxicity. Nobiletin (Nob) is a polymethoxylated flavon...

Myricetin inhibits NLRP3 inflammasome activation via reduction of ROS-dependent ubiquitination of ASC and promotion of ROS-independent NLRP3 ubiquitination.

Myricetin is a plant-derived flavonoid that exhibits diverse pharmacological properties. The NLRP3 (NLR family, pyrin domain-containing 3 protein) inflammasome is a cytosolic multiprotein complex that...

Plasma cathelicidin and longitudinal lung function in current and former smokers.

Cathelicidin (also known as LL-37 in humans) is an antimicrobial peptide secreted by epithelial and immune cells and regulated by vitamin D. The immunological roles of cathelicidin make it a putative ...

Clinical Trials [3708 Associated Clinical Trials listed on BioPortfolio]

Research to Improve Smoke Alarm Functioning and Maintenance

The purpose of this study to evaluate whether (1) targeted smoke alarm education, (2) general fire safety education with a smoke alarm component, (3) basic fire safety education, or (4) an...

Outcomes and User Acceptance of the IntelliVue Alarm Advisor Software (Europe)

This Clinical Study will be conducted as a comparative study focusing on usability and efficiency by comparing alarm burden pre- and post-implementation of an "Alarm Advisor software".

Enuresis Alarm - Is a Manual Trigger System Beneficial?

The purpose of this study is to evaluate whether the bedwetting alarm trigger activated by parents to wake their child, in addition to the moisture alarm, will improve treatment success co...

Quality Improvement - Monitoring Alarm Optimization Study

This project aims to reduce the frequency of duplicate, false and clinically insignificant alarms in hospital units, and subsequent alarm fatigue resulting from excessive alarm frequency. ...

Outcomes and User Acceptance of the IntelliVue Alarm Advisor Software (USA)

This Clinical Study will be conducted as a comparative study focusing on usability and efficiency by comparing alarm burden pre- and post- implementation of an "Alarm Advisor software".

Medical and Biotech [MESH] Definitions

Specialized clothing or equipment worn for protection against health hazards. Personal Protective Equipment may include MASKS; RESPIRATORY PROTECTIVE DEVICES; HEAD PROTECTIVE DEVICES; EYE PROTECTIVE DEVICES; EAR PROTECTIVE DEVICES; PROTECTIVE CLOTHING; and protective footwear.

A form of bronchial disorder with three distinct components: airway hyper-responsiveness (RESPIRATORY HYPERSENSITIVITY), airway INFLAMMATION, and intermittent AIRWAY OBSTRUCTION. It is characterized by spasmodic contraction of airway smooth muscle, WHEEZING, and dyspnea (DYSPNEA, PAROXYSMAL).

Professional or volunteer members of a fire department who are trained to suppress fire and respond to related emergency.

The structural changes in the number, mass, size and/or composition of the airway tissues.

Evaluation, planning, and use of a range of procedures and airway devices for the maintenance or restoration of a patient's ventilation.

Advertisement
Quick Search
Advertisement
Advertisement

 


DeepDyve research library

Relevant Topics

Infectious-diseases
Antiretroviral Therapy Clostridium Difficile Ebola HIV & AIDS Infectious Diseases Influenza Malaria Measles Sepsis Swine Flu Tropical Medicine Tuberculosis Infectious diseases are caused by pathogenic...

Pulmonary
Pulmonary relating to or associated with the lungs eg Asthma, chronic bronchitis, emphysema, COPD, Cystic Fibrosis, Influenza,  Lung Cancer, Pneumonia, Pulmonary Arterial Hypertension, Sleep Disorders etc Follow and track Lung Cancer News ...


Searches Linking to this Article