Department of Biomedical Sciences and Pathobiology, College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
Graduate Program in Translational Biology, Medicine, and Health, Virginia Tech, Roanoke, VA, United States.
Front Immunol. 2022 Jul 28;13:923754. doi: 10.3389/fimmu.2022.923754. eCollection 2022.
Commensal bacteria and the immune system have a close and strong relationship that maintains a balance to control inflammation. Alterations of the microbiota, known as dysbiosis, can direct reactivity to self-antigens not only in the intestinal mucosa but also at the systemic level. Our laboratory previously reported gut dysbiosis, particularly lower abundance of bacteria in the family , in lupus-prone MRL/ mice, a model of systemic autoimmunity. Restoring the microbiota with a mix of 5 different species (spp.), and , attenuated lupus-liked clinical signs, including splenomegaly and lymphadenopathy. However, our understanding of the mechanism was limited. In this study, we first investigated the effects of individual species. Surprisingly, none of the species individually recapitulated the benefits of the mix. Instead, spp. acted synergistically to attenuate splenomegaly and renal lymphadenopathy through secreted factors and a CXCR1-dependent mechanism. Interestingly, oral administration of MRS broth exerted the same benefits likely through increasing the relative abundance of endogenous spp. Mechanistically, we found increased percentages of FOXP3-negative type 1 regulatory T cells with administration of the mix in both spleen and mesenteric lymph nodes. In addition, oral gavage of spp. decreased the percentage of central memory T cells while increasing that of effector memory T cells in the lymphoid organs. Furthermore, a decreased percentage of double negative T cells was observed in the spleen with the mix. These results suggest that spp. might act on T cells to attenuate splenomegaly and lymphadenopathy. Together, this study advances our understanding of how spp. attenuate lupus in MRL/ mice. The synergistic action of these bacteria suggests that multiple probiotic bacteria in combination may dampen systemic autoimmunity and benefit lupus patients.
共生细菌与免疫系统之间存在着密切而强大的关系，这种关系可以维持平衡，控制炎症。微生物群落的改变，即所谓的失调，不仅可以使肠道黏膜，还可以使全身的自身抗原产生反应性。我们的实验室之前报道过肠道微生物失调，特别是在易患狼疮的 MRL/小鼠中，家族细菌的丰度降低，这是一种系统性自身免疫的模型。用 5 种不同的细菌（ spp.）混合物恢复微生物群，可以减轻类似于狼疮的临床症状，包括脾肿大和淋巴结病。然而，我们对其机制的理解是有限的。在这项研究中，我们首先研究了单个物种的影响。令人惊讶的是，没有一个物种可以单独重现混合物的益处。相反， spp. 通过分泌因子和 CXCR1 依赖性机制协同作用，减轻脾肿大和肾淋巴结病。有趣的是，口服 MRS 肉汤可能通过增加内源性 spp. 的相对丰度来发挥同样的益处。从机制上讲，我们发现，在用混合物处理后，无论是在脾脏还是肠系膜淋巴结中，FOXP3 阴性的 1 型调节性 T 细胞的比例都增加了。此外， spp. 的口服灌胃降低了淋巴器官中中央记忆 T 细胞的比例，而增加了效应记忆 T 细胞的比例。此外，在脾脏中，双阴性 T 细胞的比例也有所下降。这些结果表明， spp. 可能通过作用于 T 细胞来减轻脾肿大和淋巴结病。总的来说，这项研究提高了我们对 spp. 如何在 MRL/小鼠中减轻狼疮的理解。这些细菌的协同作用表明，多种益生菌的组合可能会抑制系统性自身免疫，并有益于狼疮患者。
