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白细胞介素-10(IL-10)由突变型中毒性休克综合征毒素 1 疫苗诱导的记忆 T 细胞产生,可下调白细胞介素-17 的产生,并消除其对金黄色葡萄球菌感染的保护作用。

Interleukin-10 (IL-10) Produced by Mutant Toxic Shock Syndrome Toxin 1 Vaccine-Induced Memory T Cells Downregulates IL-17 Production and Abrogates the Protective Effect against Staphylococcus aureus Infection.

机构信息

Department of Microbiology and Immunology, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.

Institute for Animal Experimentation, Hirosaki University Graduate School of Medicine, Hirosaki, Aomori, Japan.

出版信息

Infect Immun. 2019 Sep 19;87(10). doi: 10.1128/IAI.00494-19. Print 2019 Oct.

Abstract

Development of long-term memory is crucial for vaccine-induced adaptive immunity against infectious diseases such as infection. Toxic shock syndrome toxin 1 (TSST-1), one of the superantigens produced by , is a possible vaccine candidate against infectious diseases caused by this pathogen. We previously reported that vaccination with less toxic mutant TSST-1 (mTSST-1) induced T helper 17 (Th17) cells and elicited interleukin-17A (IL-17A)-mediated protection against infection 1 week after vaccination. In the present study, we investigated the host immune response induced by mTSST-1 vaccination in the memory phase, 12 weeks after the final vaccination. The protective effect and IL-17A production after vaccination with mTSST-1 were eliminated because of IL-10 production. In the presence of IL-10-neutralizing monoclonal antibody (mAb), IL-17A production was restored in culture supernatants of CD4 T cells and macrophages sorted from the spleens of vaccinated mice. Vaccinated mice treated with anti-IL-10 mAb were protected against systemic infection in the memory phase. From these results, it was suggested that IL-10 produced in the memory phase suppresses the IL-17A-dependent vaccine effect through downregulation of IL-17A production.

摘要

长期记忆的发展对于疫苗诱导的抗感染免疫至关重要,如感染。毒性休克综合征毒素 1(TSST-1)是由产生的超抗原之一,是针对这种病原体引起的传染病的一种潜在疫苗候选物。我们之前报道过,接种毒性较低的突变 TSST-1(mTSST-1)可诱导 T 辅助 17(Th17)细胞,并在接种后 1 周通过白细胞介素-17A(IL-17A)介导的保护作用抵抗感染。在本研究中,我们在记忆期(最后一次接种后 12 周)研究了 mTSST-1 接种引起的宿主免疫反应。由于产生了白细胞介素-10(IL-10),mTSST-1 接种的保护作用和 IL-17A 产生被消除。在存在中和 IL-10 的单克隆抗体(mAb)的情况下,从接种小鼠脾脏中分离的 CD4 T 细胞和巨噬细胞的培养上清液中恢复了 IL-17A 的产生。用抗 IL-10 mAb 处理的接种小鼠在记忆期免受全身性感染。从这些结果表明,在记忆期产生的 IL-10 通过下调 IL-17A 的产生来抑制 IL-17A 依赖性疫苗效应。

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