Abstract

Numerous researchers have described the potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of various infectious and inflammatory diseases. However, contrary to what has been reported, the transplantation of BM-MSCs in a mouse model of Paracoccidioides brasiliensis-induced pulmonary fibrosis exacerbated the inflammatory process and fibrosis, worsening the course of the infection. The aim of this work was to determine whether P. brasiliensis exerts an immunomodulatory effect on BM-MSCs. The results indicate that P. brasiliensis can activate BM-MSCs through a mechanism dependent on TLR2, TLR4 and Dectin-1. In addition, it was found that these fungal cells can adhere and internalize within BM-MSCs. Nonetheless, this process did not affect the survival of the fungus and on the contrary, triggered the expression of inflammatory mediators such as IL-6, IL-17, TNF-α, and TGF-β. The present findings correlate with the loss of a fungicidal effect and poor control of the fungus, evidenced by the count of the colony-forming units. Previously reported in vivo results are thus confirmed, showing that P. brasiliensis induces an inflammatory profile in BM-MSCs when producing pro-inflammatory molecules that amplify such response.Numerous researchers have described the potential of bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of various infectious and inflammatory diseases. However, contrary to what has been reported, the transplantation of BM-MSCs in a mouse model of Paracoccidioides brasiliensis-induced pulmonary fibrosis exacerbated the inflammatory process and fibrosis, worsening the course of the infection. The aim of this work was to determine whether P. brasiliensis exerts an immunomodulatory effect on BM-MSCs. The results indicate that P. brasiliensis can activate BM-MSCs through a mechanism dependent on TLR2, TLR4 and Dectin-1. In addition, it was found that these fungal cells can adhere and internalize within BM-MSCs. Nonetheless, this process did not affect the survival of the fungus and on the contrary, triggered the expression of inflammatory mediators such as IL-6, IL-17, TNF-α, and TGF-β. The present findings correlate with the loss of a fungicidal effect and poor control of the fungus, evidenced by the count of the colony-forming units. Previously reported in vivo results are thus confirmed, showing that P. brasiliensis induces an inflammatory profile in BM-MSCs when producing pro-inflammatory molecules that amplify such response.

中文翻译：

---

Paracoccidioides brasiliensis 通过 TLR2、TLR4 和 Dectin-1 激活间充质干细胞

摘要

许多研究人员已经描述了骨髓间充质干细胞 (BM-MSCs) 在治疗各种感染性和炎症性疾病方面的潜力。然而，与已报道的相反，在巴西拟球孢子虫诱导的肺纤维化小鼠模型中移植 BM-MSC加剧了炎症过程和纤维化，使感染过程恶化。这项工作的目的是确定巴西假单胞菌是否对 BM-MSC 发挥免疫调节作用。结果表明，P. brasiliensis可以通过依赖于 TLR2、TLR4 和 Dectin-1 的机制激活 BM-MSC。此外，发现这些真菌细胞可以在 BM-MSC 内粘附和内化。尽管如此，这个过程并不影响真菌的存活，相反，它触发了炎症介质如 IL-6、IL-17、TNF-α 和 TGF-β 的表达。目前的发现与杀真菌作用的丧失和真菌控制不佳相关，由菌落形成单位的计数证明。先前报道的体内结果因此得到证实，表明P. brasiliensis当产生放大这种反应的促炎分子时，在 BM-MSC 中诱导炎症特征。许多研究人员描述了骨髓间充质干细胞 (BM-MSC) 治疗各种感染和炎症疾病的潜力。然而，与已报道的相反，在巴西拟球孢子虫诱导的肺纤维化小鼠模型中移植 BM-MSC加剧了炎症过程和纤维化，使感染过程恶化。这项工作的目的是确定巴西假单胞菌是否对 BM-MSC 发挥免疫调节作用。结果表明，P. brasiliensis可以通过依赖于 TLR2、TLR4 和 Dectin-1 的机制激活 BM-MSC。此外，发现这些真菌细胞可以在 BM-MSC 内粘附和内化。尽管如此，这个过程并不影响真菌的存活，相反，它触发了炎症介质如 IL-6、IL-17、TNF-α 和 TGF-β 的表达。目前的发现与杀真菌作用的丧失和真菌控制不佳相关，由菌落形成单位的计数证明。先前报道的体内结果因此得到证实，表明巴西假单胞菌在产生放大这种反应的促炎分子时会在 BM-MSC 中诱导炎症特征。