Department of Bacteriology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal-Ale-Ahmad Ave., 14117-13116, Tehran, Iran.
Department of Immunology, Faculty of Medical Sciences, Tarbiat Modares University, Jalal-Ale-Ahmad Ave., 14117-13116, Tehran, Iran.
Stem Cell Res Ther. 2021 Nov 3;12(1):564. doi: 10.1186/s13287-021-02622-0.
Vibrio cholerae is the causative agent of cholera, which is commonly associated with high morbidity and mortality, and presents a major challenge to healthcare systems throughout the world. Lipopolysaccharide (LPS) is required for full protection against V. cholerae but can induce inflammation and septic shock. Mesenchymal stem cells (MSCs) are currently used to treat infectious and inflammatory diseases. Therefore, this study aimed to evaluate the immune-modulating effects of the LPS-MSC-conditioned medium (CM) on V. cholerae LPS immunization in a murine model.
After preconditioning MSCs with LPS, mice were immunized intraperitoneally on days 0 and 14 with the following combinations: LPS + LPS-MSC-CM; detoxified LPS (DLPS) + MSC-CM; LPS + MSC sup; LPS; LPS-MSC-CM; MSC supernatant (MSC sup); and PBS. The mouse serum and saliva samples were collected to evaluate antibody (serum IgG and saliva IgA) and cytokine responses (TNF-α, IL-10, IL-6, TGF-β, IL-4, IL-5, and B-cell activating factor (BAFF)).
The LPS + LPS-MSC-CM significantly increased total IgG and IgA compared to other combinations (P < 0.001). TNF-α levels, in contrast to IL-10 and TGF-β, were reduced significantly in mice receiving the LPS + LPS-MSC-CM compared to mice receiving only LPS. IL-4, IL-5, and BAFF levels significantly increased in mice receiving increased doses of LPS + LPS-MSC-CM compared to those who received only LPS. The highest vibriocidal antibody titer (1:64) was observed in LPS + LPS-MSC-CM-immunized mice and resulted in a significant improvement in survival in infant mice infected by V. cholerae O1.
The LPS-MSC-CM modulates the immune response to V. cholerae LPS by regulating inflammatory and anti-inflammatory responses and inducing vibriocidal antibodies, which protect neonate mice against V. cholerae infection.
霍乱弧菌是霍乱的病原体，常伴有高发病率和死亡率，对全球的医疗体系构成重大挑战。脂多糖（LPS）是预防霍乱弧菌感染的必要条件，但可诱导炎症和感染性休克。间充质干细胞（MSCs）目前被用于治疗感染和炎症性疾病。因此，本研究旨在评估 LPS-MSC 条件培养基（CM）对 LPS 免疫的霍乱弧菌 LPS 免疫小鼠模型的免疫调节作用。
用 LPS 预处理 MSC 后，在第 0 天和第 14 天通过腹腔注射以下组合对小鼠进行免疫：LPS+LPS-MSC-CM；脱毒 LPS（DLPS）+MSC-CM；LPS+MSC 上清（MSC sup）；LPS；LPS-MSC-CM；MSC 上清液（MSC sup）；和 PBS。收集小鼠血清和唾液样本，以评估抗体（血清 IgG 和唾液 IgA）和细胞因子反应（TNF-α、IL-10、IL-6、TGF-β、IL-4、IL-5 和 B 细胞激活因子（BAFF））。
与其他组合相比，LPS+LPS-MSC-CM 显著增加了总 IgG 和 IgA（P<0.001）。与单独 LPS 相比，接受 LPS+LPS-MSC-CM 的小鼠 TNF-α 水平显著降低，而 IL-10 和 TGF-β 水平升高。与单独 LPS 相比，接受更高剂量 LPS+LPS-MSC-CM 的小鼠 IL-4、IL-5 和 BAFF 水平显著升高。在 LPS+LPS-MSC-CM 免疫的小鼠中观察到最高的杀菌抗体滴度（1:64），并显著提高了感染霍乱弧菌 O1 的新生儿小鼠的存活率。
LPS-MSC-CM 通过调节炎症和抗炎反应以及诱导杀菌抗体来调节对 LPS 的免疫反应，从而保护新生儿小鼠免受霍乱弧菌感染。
