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合成的与血清型 3 荚膜多糖相关的 BSA 缀合二糖增加了小鼠中的 IL-17A 水平、γδ T 细胞和 B1 细胞。

Synthetic BSA-conjugated disaccharide related to the serotype 3 capsular polysaccharide increases IL-17A Levels, γδ T cells, and B1 cells in mice.

机构信息

Laboratory of Therapeutic Vaccines, Mechnikov Research Institute for Vaccines and Sera, Moscow, Russia.

Laboratory of Glycoconjugate Chemistry, N. D. Zelinsky Institute of Organic Chemistry, Russian Academy of Science, Moscow, Russia.

出版信息

Front Immunol. 2024 May 22;15:1388721. doi: 10.3389/fimmu.2024.1388721. eCollection 2024.

Abstract

The disaccharide (β-D-glucopyranosyluronic acid)-(1→4)-β-D-glucopyranoside represents a repeating unit of the capsular polysaccharide of serotype 3. A conjugate of the disaccharide with BSA (di-BSA conjugate) adjuvanted with aluminum hydroxide induced - in contrast to the non-adjuvanted conjugate - IgG1 antibody production and protected mice against serotype 3 infection after intraperitoneal prime-boost immunization. Adjuvanted and non-adjuvanted conjugates induced production of Th1 (IFNγ, TNFα); Th2 (IL-5, IL-13); Th17 (IL-17A), Th1/Th17 (IL-22), and Th2/Th17 cytokines (IL-21) after immunization. The concentration of cytokines in mice sera was higher in response to the adjuvanted conjugate, with the highest level of IL-17A production after the prime and boost immunizations. In contrast, the non-adjuvanted conjugate elicited only weak production of IL-17A, which gradually decreased after the second immunization. After boost immunization of mice with the adjuvanted di-BSA conjugate, there was a significant increase in the number of CD45+/CD19+ B cells, TCR+ γδ T cell, CD5+ В1 cells, and activated cells with MHC II+ expression in the spleens of the mice. IL-17A, TCR+ γδ T cells, and CD5+ В1 cells play a crucial role in preventing pneumococcal infection, but can also contribute to autoimmune diseases. Immunization with the adjuvanted and non-adjuvanted di-BSA conjugate did not elicit autoantibodies against double-stranded DNA targeting cell nuclei in mice. Thus, the molecular and cellular markers associated with antibody production and protective activity in response to immunization with the di-BSA conjugate adjuvanted with aluminum hydroxide are IL-17A, TCR+ γδ T cells, and CD5+ В1 cells against the background of increasing MHC II+ expression.

摘要

该二糖(β-D-吡喃葡萄糖醛酸基)-(1→4)-β-D-吡喃葡萄糖苷代表 3 型荚膜多糖的重复单元。与非佐剂缀合物相比,用氢氧化铝佐剂的二糖与 BSA(双-BSA 缀合物)缀合诱导了 IgG1 抗体的产生,并在腹腔内进行初免-加强免疫接种后保护了小鼠免受 3 型感染。佐剂和非佐剂缀合物在免疫后诱导产生了 Th1(IFNγ、TNFα);Th2(IL-5、IL-13);Th17(IL-17A)、Th1/Th17(IL-22)和 Th2/Th17 细胞因子(IL-21)。佐剂缀合物的反应中,血清细胞因子的浓度更高,初免和加强免疫后产生的 IL-17A 水平最高。相比之下,非佐剂缀合物仅诱导出较弱的 IL-17A 产生,且在第二次免疫后逐渐减少。用佐剂双-BSA 缀合物加强免疫后,小鼠脾脏中 CD45+/CD19+B 细胞、TCR+γδ T 细胞、CD5+В1 细胞和 MHC II+表达的活化细胞数量显著增加。IL-17A、TCR+γδ T 细胞和 CD5+В1 细胞在预防肺炎球菌感染方面起着至关重要的作用,但也可能导致自身免疫性疾病。用佐剂和非佐剂双-BSA 缀合物免疫不会引起针对细胞核的双链 DNA 自身抗体。因此,与用氢氧化铝佐剂佐剂的双-BSA 缀合物免疫相关的与抗体产生和保护活性相关的分子和细胞标记物是 IL-17A、TCR+γδ T 细胞和 CD5+В1 细胞,其背景是 MHC II+表达增加。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5aa3/11150546/7c856110a576/fimmu-15-1388721-g001.jpg

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