Department of Infectious Diseases, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
Core Facilities, Zhejiang University School of Medicine, Hangzhou, China.
Cell Prolif. 2019 Mar;52(2):e12565. doi: 10.1111/cpr.12565. Epub 2019 Feb 7.
The lung-gut axis is known to be involved in the pathogenesis of Staphylococcus aureus pneumonia. However, the underlying mechanisms remain unclear. We examined the role of pulmonary mast cells (MCs) in the regulation of the lung-gut axis during S. aureus pneumonia.
We created a mouse model of S. aureus pneumonia using MC-deficient mice (Kit ) and examined the level of inflammation, bacterial burden, expression of cathelicidin-related antimicrobial peptide (CRAMP) and composition of the gut microbiota. We further evaluated anti-bacterial immunity by administering bone marrow MCs (BMMCs) or CRAMP into the lungs of Kit mice.
After S. aureus challenge, the MC-deficient mice, compared with wild-type (WT) mice, displayed attenuated lung inflammation, decreased expression of CRAMP, higher bacterial lung load and disturbance of the intestinal microbiota. Adoptive transfer of BMMCs into the lung effectively reconstituted the host defence against S. aureus in Kit mice, thus resulting in recovery of S. aureus pneumonia-induced intestinal dysfunction. Similarly, exogenous administration of CRAMP significantly enhanced anti-bacterial immunity in the lungs of MC-deficient mice.
This study provides evidence for the involvement of MCs in the regulation of the lung-gut axis during S. aureus pneumonia.
已知肺-肠轴参与金黄色葡萄球菌肺炎的发病机制。然而，其潜在机制尚不清楚。我们研究了肺部肥大细胞（MCs）在金黄色葡萄球菌肺炎期间调节肺-肠轴中的作用。
我们使用 MC 缺陷小鼠（Kit ）建立了金黄色葡萄球菌肺炎小鼠模型，并检测了炎症水平、细菌负荷、抗菌肽相关肽（CRAMP）的表达和肠道微生物组的组成。我们进一步通过将骨髓 MC（BMMCs）或 CRAMP 注入 Kit 小鼠的肺部来评估抗细菌免疫。
金黄色葡萄球菌攻击后，与野生型（WT）小鼠相比，MC 缺陷小鼠肺部炎症减轻，CRAMP 表达降低，细菌肺部负荷增加，肠道微生物组失调。将 BMMCs 转移到肺部可有效重建 Kit 小鼠对金黄色葡萄球菌的宿主防御，从而恢复金黄色葡萄球菌肺炎引起的肠道功能障碍。同样，外源性给予 CRAMP 可显著增强 MC 缺陷小鼠肺部的抗细菌免疫。
本研究为 MCs 在金黄色葡萄球菌肺炎期间调节肺-肠轴提供了证据。
