Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA.
Autoimmunity. 2020 Sep;53(6):323-332. doi: 10.1080/08916934.2020.1777282. Epub 2020 Jun 19.
Although the relationship between autoimmunity and microorganisms is complex, there is evidence that microorganisms can prevent the development of various autoimmune diseases. Lactobacilli are beneficial gut bacteria that play an important role in immune system development. The goals of this study were to assess the ability of three different strains of lactobacilli ( B255, DSM 17509 and LP299v) to control lupus development/progression in (NZBxNZW)F1 (BWF1) lupus-prone mice before and after disease onset, and identify the mechanisms mediating protection. BWF1 mice fed with individual or before disease onset exhibited delayed lupus onset and increased survival, while feeding had little impact. treatment of BWF1 dendritic cells with individual lactobacilli strains upregulated IL-10 production to various extents, with being the most effective. The protection mediated by was associated with upregulation of B7-1 and B7-2 by antigen presenting cells, two costimulatory molecules important for regulatory T cell (Treg) induction. Moreover, feeding lead to increased percentages of CD4Foxp3 Tregs and IL10-producing T cells in the lymphoid organs of treated mice. More importantly, mice fed after disease onset remained stable for several months, i.e. exhibited delayed anti-nucleic acid production and kidney disease progression, and increased survival. Therefore, feeding lactobacilli appears to delay lupus progression possibly mechanisms involving Treg induction and IL-10 production. Altogether, these data support the notion that ingestion of lactobacilli, with immunoregulatory properties, may be a viable strategy for controlling disease development and progression in patients with lupus, i.e. extending remission length and reducing flare frequency.
尽管自身免疫与微生物之间的关系很复杂，但有证据表明微生物可以预防多种自身免疫性疾病的发生。乳杆菌是有益的肠道细菌，在免疫系统发育中起着重要作用。本研究的目的是评估三种不同的乳杆菌（B255、DSM17509 和 LP299v）在疾病发病前和发病后控制（NZBxNZW）F1（BWF1）狼疮易感小鼠狼疮发生/进展的能力，并确定介导保护的机制。在疾病发病前用单独的或进行喂食的 BWF1 小鼠表现出狼疮发病延迟和存活率增加，而用进行喂食的影响较小。用单独的乳杆菌菌株处理 BWF1 树突状细胞可不同程度地上调 IL-10 的产生，其中效果最显著。通过 进行的保护与抗原呈递细胞上调 B7-1 和 B7-2 有关，B7-1 和 B7-2 是诱导调节性 T 细胞（Treg）的两个重要共刺激分子。此外，喂食 导致治疗小鼠的淋巴器官中 CD4Foxp3 Treg 和产生 IL10 的 T 细胞的百分比增加。更重要的是，在疾病发病后用进行喂食的小鼠保持稳定数月，即表现出抗核酸产生和肾脏疾病进展延迟，以及存活率增加。因此，用乳杆菌进行喂食似乎可以延迟狼疮的进展，可能通过诱导 Treg 和产生 IL-10 的机制。总之，这些数据支持这样的观点，即摄入具有免疫调节特性的乳杆菌可能是控制狼疮患者疾病发生和进展的可行策略，即延长缓解期长度和减少发作频率。
