Medical Clinic III for Pneumology, Allergology, Sleep- and Respiratory Medicine, Bergmannsheil University Hospital, Bürkle-de-la-Camp-Platz 1, 44789, Bochum, Germany.
Department of Pneumology, Clinic III for Internal Medicine, University of Cologne, Cologne, Germany.
J Mol Med (Berl). 2019 Jun;97(6):817-828. doi: 10.1007/s00109-019-01778-w. Epub 2019 Mar 30.
COPD patients have an increased susceptibility to bacterial airway infections that can induce exacerbations. In response to infections, circulating monocytes become recruited to the infected tissue and secrete cytokines. We hypothesized that this cytokine response is reduced in COPD. Cultured peripheral blood monocytes of never smokers (NS) and smokers without (S) and with COPD (3 study populations, n = 36-37) were stimulated with extracts of Haemophilus influenzae, Staphylococcus aureus, or Streptococcus pneumoniae or with four different pathogen-associated molecular patterns (PAMPs). Four cytokines and 9 PAMP-related signaling molecules were measured and compared between the groups. Granulocyte-macrophage-colony-stimulating-factor responses to all stimulants were reduced in S and COPD compared to NS. Tumor-necrosis-factor-α responses to all bacterial extracts, peptidoglycan, and lipopolysaccharide were reduced in S and/or COPD. Interleukin-10 responses to S. aureus and lipoteichoic acid were increased in COPD. Correlations to pack-years and lung function were found. The peptidoglycan-receptor NOD2 and the mRNA of the lipopolysaccharide-receptor TLR4 were reduced in S and COPD. Cytokine responses of monocytes to bacteria are suppressed by smoking and in COPD possibly due to NOD2 and TLR4 reduction and/or interleukin-10 increase. This might help to explain the increased susceptibility to bacterial infections. These systemic molecular pathologies might be targets for therapeutic strategies to prevent infection-induced exacerbations. KEY MESSAGES: COPD subjects have an increased susceptibility to bacterial infections. This implies defects in the immune response to bacteria and is critical for disease progression. The cytokine response of monocytes to bacteria is reduced in COPD. This might be due to a reduced NOD2 and TLR4 and an increased IL-10 expression. This can explain the increased susceptibility to infections and help to identify drug targets.
COPD 患者对细菌气道感染的易感性增加，这可能导致病情恶化。为了应对感染，循环中的单核细胞被招募到感染组织并分泌细胞因子。我们假设 COPD 患者的这种细胞因子反应会降低。我们用从未吸烟的人（NS）和没有 COPD 的吸烟者（S）以及有 COPD 的吸烟者（3 个研究人群，n = 36-37）的外周血单核细胞进行培养，然后用流感嗜血杆菌、金黄色葡萄球菌或肺炎链球菌的提取物或 4 种不同的病原体相关分子模式（PAMPs）进行刺激。我们在这些组之间对 4 种细胞因子和 9 种 PAMP 相关的信号分子进行了测量和比较。与 NS 相比，S 和 COPD 患者对所有刺激物的粒细胞巨噬细胞集落刺激因子反应都降低了。S 和/或 COPD 患者对所有细菌提取物、肽聚糖和脂多糖的肿瘤坏死因子-α反应都降低了。肺炎球菌和脂磷壁酸引起的 COPD 患者白细胞介素-10 反应增加了。还发现了与吸烟量和肺功能的相关性。S 和 COPD 患者的肽聚糖受体 NOD2 和脂多糖受体 TLR4 的 mRNA 减少了。单核细胞对细菌的细胞因子反应受到吸烟和 COPD 的抑制，这可能是由于 NOD2 和 TLR4 减少和/或白细胞介素-10 增加所致。这可能有助于解释对细菌感染的易感性增加。这些系统性分子病理学可能是预防感染性加重的治疗策略的靶点。关键信息：COPD 患者易发生细菌感染。这意味着对细菌的免疫反应存在缺陷，这对疾病进展至关重要。COPD 患者的单核细胞对细菌的细胞因子反应降低。这可能是由于 NOD2 和 TLR4 减少以及 IL-10 表达增加所致。这可以解释易感染的原因，并有助于确定药物靶点。
