肺炎相关重症哮喘表型的新疗法
2020/09/18
摘要
明确的队列研究中出现了明显的哮喘表型，并且似乎与肺炎史有关。哮喘患者更易受到肺炎链球菌的感染;然而，对这一病原体免疫缺陷的机制仍未阐明。在这里，我们讨论哮喘患者中的交替活化巨噬细胞(AAMs)是如何导致细菌吞噬功能缺陷的，以及呼吸道病毒是如何破坏基本的宿主免疫，导致细菌扩散到肺。我们还描述了呼吸系统病原体如何诱导中性粒细胞炎症和放大哮喘患者的2型炎症。最后，我们提出了新的双重作用策略，包括粒细胞集落刺激因子受体(G-CSFR)拮抗剂和特异性分解介质(SPMs)抑制2型和中性粒细胞炎症，而不影响病原体的清除。
Novel Therapies for Pneumonia-Associated Severe Asthma Phenotypes
Angelica Papanicolaou, Hao Wang , Catherine Satzke, Ross Vlahos, Nick Wilson , Steven Bozinovski
Abstract
Distinct asthma phenotypes are emerging from well-defined cohort studies and appear to be associated with a history of pneumonia. Asthmatics are more susceptible to infections caused by Streptococcus pneumoniae; however, the mechanisms that underlie defective immunity to this pathogen are still being elucidated. Here, we discuss how alternatively activated macrophages (AAMs) in asthmatics are defective in bacterial phagocytosis and how respiratory viruses disrupt essential host immunity to cause bacterial dispersion deeper into the lungs. We also describe how respiratory pathogens instigate neutrophilic inflammation and amplify type-2 inflammation in asthmatics. Finally, we propose novel dual-acting strategies including granulocyte-colony-stimulating factor receptor (G-CSFR) antagonism and specialised pro-resolving mediators (SPMs) to suppress type-2 and neutrophilic inflammation without compromising pathogen clearance.
明确的队列研究中出现了明显的哮喘表型，并且似乎与肺炎史有关。哮喘患者更易受到肺炎链球菌的感染;然而，对这一病原体免疫缺陷的机制仍未阐明。在这里，我们讨论哮喘患者中的交替活化巨噬细胞(AAMs)是如何导致细菌吞噬功能缺陷的，以及呼吸道病毒是如何破坏基本的宿主免疫，导致细菌扩散到肺。我们还描述了呼吸系统病原体如何诱导中性粒细胞炎症和放大哮喘患者的2型炎症。最后，我们提出了新的双重作用策略，包括粒细胞集落刺激因子受体(G-CSFR)拮抗剂和特异性分解介质(SPMs)抑制2型和中性粒细胞炎症，而不影响病原体的清除。
(中日友好医院呼吸与危重症医学科 张清 摘译 林江涛 审校)
(Trends Mol Med. 2020 Aug 19;S1471-4914(20)30185-4.doi:10.1016/j.molmed.2020.07.006. Online ahead of print.)
(Trends Mol Med. 2020 Aug 19;S1471-4914(20)30185-4.doi:10.1016/j.molmed.2020.07.006. Online ahead of print.)
Novel Therapies for Pneumonia-Associated Severe Asthma Phenotypes
Angelica Papanicolaou, Hao Wang , Catherine Satzke, Ross Vlahos, Nick Wilson , Steven Bozinovski
Abstract
Distinct asthma phenotypes are emerging from well-defined cohort studies and appear to be associated with a history of pneumonia. Asthmatics are more susceptible to infections caused by Streptococcus pneumoniae; however, the mechanisms that underlie defective immunity to this pathogen are still being elucidated. Here, we discuss how alternatively activated macrophages (AAMs) in asthmatics are defective in bacterial phagocytosis and how respiratory viruses disrupt essential host immunity to cause bacterial dispersion deeper into the lungs. We also describe how respiratory pathogens instigate neutrophilic inflammation and amplify type-2 inflammation in asthmatics. Finally, we propose novel dual-acting strategies including granulocyte-colony-stimulating factor receptor (G-CSFR) antagonism and specialised pro-resolving mediators (SPMs) to suppress type-2 and neutrophilic inflammation without compromising pathogen clearance.
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骨膜蛋白:哮喘患者气道上皮功能异常的原因?
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农业肺健康研究中DNA甲基化与成人哮喘的表观基因组相关性研究
