Division of Cellular and Molecular Engineering, Department of Life Technology and Science, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan.
Division of Virology, Department of Infection and Immunity, Faculty of Medicine, Jichi Medical University, Shimotsuke, Tochigi, Japan.
Front Immunol. 2024 Mar 27;15:1335975. doi: 10.3389/fimmu.2024.1335975. eCollection 2024.
Lactic acid bacteria (LAB) possess the ability to argument T cell activity through functional modification of antigen presenting cells (APCs), such as dendritic cells (DCs) and macrophages. Nevertheless, the precise mechanism underlying LAB-induced enhancement of antigen presentation in APCs remains incompletely understood. To address this question, we investigated the detailed mechanism underlying the enhancement of major histocompatibility complex (MHC) class I-restricted antigen presentation in DCs using a probiotic strain known as subsp. C60. We found that Heat-killed-C60 (HK-C60) facilitated the processing and presentation of ovalbumin (OVA) peptide antigen OVA (SIINFEKL) via H-2K in bone marrow-derived dendritic cells (BMDCs), leading to increased generation of effector CD8+ T cells both and . We also revealed that HK-C60 stimulation augmented the activity of 20S immunoproteasome (20SI) in BMDCs, thereby enhancing the MHC class I-restricted antigen presentation machinery. Furthermore, we assessed the impact of HK-C60 on CD8+ T cell activation in an OVA-expressing B16-F10 murine melanoma model. Oral administration of HK-C60 significantly attenuated tumor growth compared to control treatment. Enhanced Ag processing and presentation machineries in DCs from both Peyer's Patches (PPs) and lymph nodes (LNs) resulted in an increased tumor antigen specific CD8+ T cells. These findings shed new light on the role of LAB in MHC class-I restricted antigen presentation and activation of CD8+ T cells through functional modification of DCs.
乳酸菌 (LAB) 通过功能性修饰抗原提呈细胞 (APC),如树突状细胞 (DC) 和巨噬细胞,具有调节 T 细胞活性的能力。然而,LAB 诱导 APC 中抗原呈递增强的确切机制尚不完全清楚。为了解决这个问题,我们使用一种已知的益生菌菌株 subsp. C60 研究了 LAB 诱导 DC 中 MHC Ⅰ类限制性抗原呈递增强的详细机制。我们发现 Heat-killed-C60 (HK-C60) 通过 H-2K 促进了骨髓来源的树突状细胞 (BMDC) 中卵清蛋白 (OVA) 肽抗原 OVA (SIINFEKL) 的加工和呈递,导致效应 CD8+ T 细胞的生成增加 both and. 我们还揭示了 HK-C60 刺激增强了 BMDC 中 20S 免疫蛋白酶体 (20SI) 的活性,从而增强了 MHC Ⅰ类限制性抗原呈递机制。此外,我们评估了 HK-C60 对 OVA 表达的 B16-F10 小鼠黑色素瘤模型中 CD8+ T 细胞激活的影响。与对照治疗相比,口服 HK-C60 可显著抑制肿瘤生长。来自派尔集合淋巴结 (PPs) 和淋巴结 (LNs) 的 DC 中增强的 Ag 加工和呈递机制导致肿瘤抗原特异性 CD8+ T 细胞增加。这些发现为 LAB 通过功能性修饰 DC 调节 MHC Ⅰ类限制性抗原呈递和激活 CD8+ T 细胞的作用提供了新的认识。