Defective Innate Immunity in Airway Disease with Prof. Louise Donnelly

“Defective Innate Immunity in Airway Diseases” presented by Prof. Louise Donnelly

As part of our ongoing seminar series, the Centre of Excellence in Severe Asthma hosted Prof. Louise Donnelly, for a webinar on “Defective Innate Immunity in Airway Diseases” on 22 November, 2017.

Presentation Summary:

Innate immune cells are a first line of defence against infection by viruses and bacteria. Innate immune cell numbers are increased in the airways of individuals with airway disease, including asthma and chronic obstructive pulmonary disease (COPD). In addition to increased cell numbers, innate cell function appears to be altered in chronic respiratory disease.

Bacterial colonisation of the lungs is increased in many patients with respiratory disease. Increased bacterial numbers are associated with increased exacerbation frequency and worse lung function. Altered innate immunity in airway diseases may help to explain the observed increase in bacteria numbers in patient populations.

Prof. Louise Donnelly provides an overview of changes in innate immunity in airway diseases, including effects on migration, cytokine production and ability to kill bacteria. Neutrophils and macrophages isolated from COPD patients have enhanced migration. Macrophages from COPD patients also produce high levels of inflammatory cytokines, which may increase lung inflammation. Macrophages isolated from patients with COPD or asthma have a reduced ability to kill bacteria, which may lead to increased bacterial infections. Differences in function are associated with altered cell signaling and differences in cell differentiation or polarisation.

Further studies are needed to understand what causes changes in innate immunity in airway diseases and whether restoring function would improve disease outcomes.

Key Points:

• Innate immune cells are present in the airways of patients with respiratory disease, including severe asthma and COPD
• A large proportion of patients with chronic respiratory disease have chronic bacterial colonisation of their lungs
• Increased bacteria numbers in the lung is associated with worse disease, including frequent exacerbations and decreased lung function
• The types of innate immune cells present differ by disease, with increased eosinophils predominant in asthma, and increased macrophages in COPD
• Neutrophils and monocytes isolated from patients with COPD have increased migration ability, but have less directed motion towards a chemokine (e.g. CXCL1)
• Alveolar macrophages from COPD or asthma patients have a reduced ability to kill bacteria
• Impaired bacterial killing is associated with increased exacerbation frequency
• The ability of macrophages isolated from COPD patients to remove dead neutrophils or fungal spores is also reduced
• Macrophage killing of bacteria is also reduced when COPD is caused by either cigarette smoke or biomass fuel exposure
• The types of macrophage present in the lungs of patients with COPD are completely different from macrophages found in healthy controls
• Circulating monocyte populations in the blood (macrophage progenitors) are similar in COPD patients and healthy controls
• Macrophages from COPD patients produce high levels of inflammatory cytokines and do not produce anti-inflammatory cytokines, regardless of the local environment
• Infection with rhinovirus (RV) or exposure to oxidative stress can further reduce the ability of macrophages to kill bacteria
• The mechanisms leading to altered function are unclear, but may involve changes in receptor function and cell signaling
• Bacteria also enter epithelial cells from COPD patients and survive, which may serve as a reservoir for bacterial infections

About Prof. Louise Donnelly:

Professor Louise Donnelly is a Professor of Respiratory Cell Biology, in the Section of Airway Disease at the National Heart and Lung Institute, Imperial College London.

Her research interests are primarily focused on the cellular profile of inflammatory lung diseases including asthma and COPD. In particular, her work investigates how inflammatory cells are altered in the disease state and how these changes can be exploited in the development of novel therapeutic strategies. To this end, Professor Donnelly’s group have established a number of human primary cell systems to investigate mechanisms of aberrant inflammation.

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