Department of Ophthalmology, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, U Nemocnice 2, 12808 Prague 2, Czech Republic.
Institute of Microbiology of the Czech Academy of Sciences, v.v.i., Prague, Videnska 1083, 14220 Prague 4, Czech Republic.
J Immunol Res. 2016;2016:5065703. doi: 10.1155/2016/5065703. Epub 2016 May 17.
The microbiota is a crucial modulator of the immune system. Here, we evaluated how its absence or reduction modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). We induced EAU in germ-free (GF) or conventionally housed (CV) mice and in CV mice treated with a combination of broad-spectrum antibiotics either from the day of EAU induction or from one week prior to induction of disease. The severity of the inflammation was assessed by fundus biomicroscopy or by histology, including immunohistology. The immunophenotyping of T cells in local and distant lymph nodes was performed by flow cytometry. We found that GF mice and mice where the microbiota was reduced one week before EAU induction were protected from severe autoimmune inflammation. GF mice had lower numbers of infiltrating macrophages and significantly less T cell infiltration in the retina than CV mice with EAU. GF mice also had reduced numbers of IFN-γ and IL-17-producing T cells and increased numbers of regulatory T cells in the eye-draining lymph nodes. These data suggest that the presence of microbiota during autoantigen recognition regulates the inflammatory response by influencing the adaptive immune response.
肠道微生物群是免疫系统的重要调节者。在这里，我们评估了其缺失或减少如何改变实验性自身免疫性葡萄膜炎（EAU）小鼠模型中的炎症反应。我们在无菌（GF）或常规饲养（CV）小鼠中诱导 EAU，并在 CV 小鼠中用广谱抗生素组合进行治疗，该抗生素组合从 EAU 诱导之日或疾病诱导前一周开始使用。通过眼底生物显微镜或组织学（包括免疫组织化学）评估炎症的严重程度。通过流式细胞术对局部和远处淋巴结中的 T 细胞进行免疫表型分析。我们发现，GF 小鼠和在 EAU 诱导前一周减少肠道微生物群的小鼠免受严重的自身免疫性炎症的侵害。GF 小鼠的浸润巨噬细胞数量较低，视网膜中的 T 细胞浸润明显少于患有 EAU 的 CV 小鼠。GF 小鼠的眼引流淋巴结中产生 IFN-γ和 IL-17 的 T 细胞数量减少，调节性 T 细胞数量增加。这些数据表明，在自身抗原识别过程中，肠道微生物群的存在通过影响适应性免疫反应来调节炎症反应。
