Background. Immunosuppressants such as cyclophosphamide (CTX) have been employed to treat a wide array of autoimmune diseases. The most unfavourable side effects of these drugs are their suppression on the antimicrobial immunity and increasing the risk of infection. As a promising substitution/adjunct, mesenchymal stem cells (MSCs) are currently being tested in several clinical trials. However, their influence on the recipients’ antimicrobial immunity remains unclear. Methods. In this study, C57BL/6 mice were treated with either CTX or MSCs, and then both the innate and adaptive immunity of the lung were determined. To investigate the influence of CTX and MSCs on the immune defence against infection, the treated mice were intranasally infected with opportunistic pathogen Haemophilus influenzae (Hi). Bacterial clearance and antibacterial immune responses were analysed. Results. Our data showed that CTX strongly inhibited the proliferation of lung immune cells, including alveolar macrophages (AMs) and T cells, whereas MSCs increased the numbers of these cells. CTX suppressed the phagocytic activity of AMs; on the contrary, MSCs enhanced it. Notably, infusion of MSCs led to a remarkable increase of regulatory T cells and Th1 cells in the lung. When infected by Hi, CTX did not significantly impair the elimination of invaded bacteria. However, MSC-treated mice exhibited accelerated bacterial clearance and moderate inflammation and tissue damage. Conclusion. Our study reported that unlike traditional immunosuppressants, modulation of MSCs on the recipient’s immune response is more elegant. It could preserve and even enhance the antimicrobial defence, suggesting that MSCs are better choice for patients with high risk of infection or those who need long-term immunosuppressive regimen.

中文翻译：

---

间充质干细胞增强肺部抗菌免疫并预防继发性细菌感染。

背景。环磷酰胺 (CTX) 等免疫抑制剂已被用于治疗多种自身免疫性疾病。这些药物最不利的副作用是它们对抗菌免疫的抑制和增加感染的风险。作为一种有前途的替代物/辅助物，间充质干细胞 (MSCs) 目前正在几项临床试验中进行测试。然而，它们对接受者抗菌免疫的影响仍不清楚。方法。在这项研究中，C57BL/6 小鼠用 CTX 或 MSCs 治疗，然后测定肺的先天性和适应性免疫。为了研究 CTX 和 MSCs 对感染免疫防御的影响，用机会性病原体鼻内感染处理过的小鼠流感嗜血杆菌（嗨）。分析了细菌清除率和抗菌免疫反应。结果。我们的数据显示，CTX 强烈抑制肺免疫细胞的增殖，包括肺泡巨噬细胞 (AMs) 和 T 细胞，而 MSCs 增加了这些细胞的数量。CTX 抑制 AMs 的吞噬活性；相反，MSCs 增强了它。值得注意的是，MSCs 的输注导致肺中调节性 T 细胞和 Th1 细胞的显着增加。当被 Hi 感染时，CTX 对入侵细菌的消除没有显着影响。然而，MSC 治疗的小鼠表现出加速的细菌清除和中度炎症和组织损伤。结论. 我们的研究报告说，与传统的免疫抑制剂不同，MSCs 对受体免疫反应的调节更加优雅。它可以保留甚至增强抗菌防御，表明MSCs是感染高风险患者或需要长期免疫抑制方案的患者的更好选择。