| Content Provider | Springer Nature : BioMed Central |
|---|---|
| Author | Diaz-Nicieza, Celia Sahyoun, Laura Michalaki, Christina Johansson, Cecilia Culley, Fiona J. |
| Abstract | Background Ageing is associated with an increased risk of lung infection and chronic inflammatory lung disease. Innate immune responses are the first line of defence in the respiratory tract, however, age-related changes to innate immunity in the lung are not fully described. Both resident haematopoietic cells, such as alveolar macrophages, and non-haematopoeitic cells, such as epithelial and endothelial cells can contribute to inflammatory and immune responses in the lung. In this study we aimed to determine the impact of ageing on early innate responses of resident cells in the lung. Results Aged and young mice were inoculated intranasally with lipopolysaccharide (LPS). After 4 h, aged mice recruited higher numbers of neutrophils to the airways and lung. This exacerbated inflammatory response was associated with higher concentrations of chemokines CXCL1, CXCL2 and CCL2 in the airways. Next, precision cut lung slices (PCLS) were stimulated ex vivo with LPS for 16 h. Gene expression of Cxcl2, Tnf and Il1b were all higher in PCLS from aged than young mice and higher levels of secretion of CXCL2 and TNF were detected. To determine which lung cells were altered by age, LPS was intranasally administered to aged and young mice and individual populations of cells isolated by FACS. RT-PCR on sorted cell populations demonstrated higher expression of inflammatory cytokines Cxcl2, Ccl2 and Tnf in epithelial cells and alveolar macrophages and higher expression of Cxcl2 by endothelial cells of aged mice compared to young. These differences in expression of pro-inflammatory cytokines did not correspond to higher levels of Tlr4 expression. Conclusions Ageing leads to a heightened neutrophilic inflammatory response in the lung after LPS exposure, and higher expression and production of pro-inflammatory cytokines by resident lung cells, including alveolar macrophages, epithelial cells and endothelial cells. The responses of multiple resident lung cell populations are altered by aging and contribute to the exacerbated inflammation in the lung following LPS challenge. This has implications for our understanding of respiratory infections and inflammation in older people. |
| Related Links | https://immunityageing.biomedcentral.com/counter/pdf/10.1186/s12979-024-00467-8.pdf |
| Ending Page | 12 |
| Page Count | 12 |
| Starting Page | 1 |
| File Format | HTM / HTML |
| ISSN | 17424933 |
| DOI | 10.1186/s12979-024-00467-8 |
| Journal | Immunity & Ageing |
| Issue Number | 1 |
| Volume Number | 21 |
| Language | English |
| Publisher | BioMed Central |
| Publisher Date | 2024-09-12 |
| Access Restriction | Open |
| Subject Keyword | Immunology Geriatrics Gerontology Aging Public Health Clinical Nutrition Antibodies Ageing Lung Infection Inflammation Innate immunity Geriatrics/Gerontology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Aging Immunology |
| Journal Impact Factor | 5.2/2023 |
| 5-Year Journal Impact Factor | 6.4/2023 |
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