Hernández-Aceves Juan A, Solano-Gálvez Sandra Georgina, Wilkins-Rodríguez Arturo A, Delgado-Domínguez José, Lozano Alberto Garcia, Cabello-Gutierrez Carlos, Huerta Lidia Flor Estela, Fragoso Gladis, Gutiérrez-Kobeh Laila, Vázquez-López Rosalino
Departamento de Inmunología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México (UNAM), Cto. Escolar, C.U., Coyoacán, Mexico City 04510, Mexico.
Unidad de Investigación UNAM-INC, División de Investigación, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico.
Pharmaceuticals (Basel). 2025 Jun 13;18(6):885. doi: 10.3390/ph18060885.
Bacterial lysates are known to modulate the immune response against respiratory infections. However, the effects of the commercial bacterial lysate Pulmonarom on dendritic cells-particularly human monocyte-derived dendritic cells (moDCs)-have not been studied. Additionally, limited data are available on the expression of Toll-like receptors (TLRs) and cytokines following stimulation with bacterial lysates. Human monocytes were isolated from buffy coats and differentiated into moDCs. Pulmonarom was lyophilized, quantified, and used to stimulate moDCs. Ultrastructural changes were evaluated using transmission electron microscopy. The expression of TLRs and selected cytokines was analyzed by flow cytometry. Pulmonarom stimulation induced morphological changes in moDCs, including an increased number of dendrites and lysosomes. It also led to the upregulation of MHC class II molecules and TLRs 2, 3, 6, and 7. Additionally, the production of IL-4, IL-6, IL-8, and MCP-1 was significantly increased. Pulmonarom promotes moDC maturation, characterized by enhanced antigen presentation capabilities and lysosomal activity, along with increased expression of specific TLRs and cytokines. These features suggest a trained immunity phenotype in moDCs, potentially improving their ability to initiate adaptive immune responses against respiratory pathogens. To our knowledge, this is the first study to investigate the immunomodulatory effects of Pulmonarom on human moDCs, providing novel insights into its potential as an immunotherapeutic adjuvant.
已知细菌裂解物可调节针对呼吸道感染的免疫反应。然而，市售细菌裂解物Pulmonarom对树突状细胞，特别是人单核细胞衍生的树突状细胞（moDCs）的影响尚未得到研究。此外，关于用细菌裂解物刺激后Toll样受体（TLRs）和细胞因子的表达数据有限。从血沉棕黄层中分离出人单核细胞并将其分化为moDCs。将Pulmonarom冻干、定量，并用于刺激moDCs。使用透射电子显微镜评估超微结构变化。通过流式细胞术分析TLRs和选定细胞因子的表达。Pulmonarom刺激诱导了moDCs的形态变化，包括树突和溶酶体数量增加。它还导致MHC II类分子以及TLRs 2、3、6和7的上调。此外，IL-4、IL-6、IL-8和MCP-1的产生显著增加。Pulmonarom促进moDC成熟，其特征是抗原呈递能力和溶酶体活性增强，以及特定TLRs和细胞因子的表达增加。这些特征表明moDCs具有训练有素的免疫表型，可能提高其启动针对呼吸道病原体的适应性免疫反应的能力。据我们所知，这是第一项研究Pulmonarom对人moDCs免疫调节作用的研究，为其作为免疫治疗佐剂的潜力提供了新的见解。
