Ageing results in an exacerbated inflammatory response to LPS by resident lung cells

IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Immunity & Ageing Pub Date : 2024-09-12 DOI:10.1186/s12979-024-00467-8
Celia Diaz-Nicieza, Laura Sahyoun, Christina Michalaki, Cecilia Johansson, Fiona J. Culley
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Abstract

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. 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. 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.
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衰老导致常驻肺细胞对 LPS 的炎症反应加剧
衰老与肺部感染和慢性炎症性肺病的风险增加有关。先天性免疫反应是呼吸道的第一道防线,然而,与年龄有关的肺部先天性免疫变化尚未得到充分描述。常驻造血细胞(如肺泡巨噬细胞)和非造血细胞(如上皮细胞和内皮细胞)都能促进肺部的炎症和免疫反应。本研究旨在确定衰老对肺部常驻细胞早期先天性反应的影响。给老年小鼠和年轻小鼠鼻内接种脂多糖(LPS)。4 小时后,老龄小鼠的气道和肺部聚集了更多的中性粒细胞。这种加剧的炎症反应与气道中更高浓度的趋化因子 CXCL1、CXCL2 和 CCL2 有关。老龄小鼠肺切片(PCLS)中 Cxcl2、Tnf 和 Il1b 的基因表达均高于年轻小鼠,且检测到 CXCL2 和 TNF 的分泌水平更高。为了确定哪些肺细胞因年龄而发生变化,给老年小鼠和年轻小鼠鼻内注射了 LPS,并通过 FACS 分离出单个细胞群。对分选的细胞群进行 RT-PCR 检测表明,与年轻小鼠相比,老年小鼠的上皮细胞和肺泡巨噬细胞中炎症细胞因子 Cxcl2、Ccl2 和 Tnf 的表达量更高,内皮细胞中 Cxcl2 的表达量也更高。这些促炎细胞因子表达的差异与 Tlr4 表达水平的升高并不对应。暴露于 LPS 后,衰老会导致肺部中性粒细胞炎症反应增强,肺部常驻细胞(包括肺泡巨噬细胞、上皮细胞和内皮细胞)表达和产生的促炎细胞因子增多。多种常驻肺细胞群的反应会因衰老而改变,并导致肺部在受到 LPS 挑战后炎症加剧。这对我们了解老年人的呼吸道感染和炎症具有重要意义。
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来源期刊
Immunity & Ageing
Immunity & Ageing GERIATRICS & GERONTOLOGY-IMMUNOLOGY
CiteScore
10.20
自引率
3.80%
发文量
55
期刊介绍: Immunity & Ageing is a specialist open access journal that was first published in 2004. The journal focuses on the impact of ageing on immune systems, the influence of aged immune systems on organismal well-being and longevity, age-associated diseases with immune etiology, and potential immune interventions to increase health span. All articles published in Immunity & Ageing are indexed in the following databases: Biological Abstracts, BIOSIS, CAS, Citebase, DOAJ, Embase, Google Scholar, Journal Citation Reports/Science Edition, OAIster, PubMed, PubMed Central, Science Citation Index Expanded, SCImago, Scopus, SOCOLAR, and Zetoc.
期刊最新文献
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