Institute for Immunology and School of Medicine, Tsinghua University, Beijing, 100084, China.
Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
Sci China Life Sci. 2021 Oct;64(10):1720-1731. doi: 10.1007/s11427-020-1862-8. Epub 2021 Jan 29.
Commensal bacteria boost serum IgG production in response to oral immunization with antigen and cholera toxin (CT) in a manner that depends on Nod2 (nucleotide-binding oligomerization domain-containing protein 2). In this study, we examined the role of intestinal lysozyme (Lyz1) in adjuvant activity of CT. We found that Lyz1 released Nod2 ligand(s) from bacteria. Lyz1 deficiency reduced the level of circulating Nod2 ligand in mice. Lyz1 deficiency also reduced the production of IgG and T-cellspecific cytokines after oral immunization in mice. Supplementing Lyz1-deficient mice with MDP restored IgG production. Furthermore, overexpression of Lyz1 in intestinal epithelium boosted the antigen-specific IgG response induced by CT. Collectively, our results indicate that Lyz1 plays an important role in mediating the immune regulatory effect of commensal bacteria through the release of Nod2 ligand(s).
共生菌通过 Nod2（核苷酸结合寡聚化结构域包含蛋白 2）依赖的方式促进血清 IgG 产生，该过程对口服免疫抗原和霍乱毒素（CT）有反应。在这项研究中，我们研究了肠溶菌酶（Lyz1）在 CT 佐剂活性中的作用。我们发现 Lyz1 从细菌中释放 Nod2 配体。Lyz1 缺乏会降低小鼠循环中 Nod2 配体的水平。Lyz1 缺乏还会降低口服免疫后小鼠 IgG 和 T 细胞特异性细胞因子的产生。用 MDP 补充 Lyz1 缺陷型小鼠可恢复 IgG 的产生。此外，肠上皮细胞中 Lyz1 的过表达可增强 CT 诱导的抗原特异性 IgG 反应。总之，我们的结果表明 Lyz1 通过释放 Nod2 配体（s）在介导共生菌的免疫调节作用方面发挥重要作用。
