人乳头瘤病毒疫苗诱导训练有素的免疫力,并在继发性 Toll 样受体刺激下调节促炎细胞因子的表达

IF 1.9 4区 医学 Q4 IMMUNOLOGY Microbiology and Immunology Pub Date : 2023-12-17 DOI:10.1111/1348-0421.13108
Mako Yamaguchi, Yohana S. Mtali, Hitomi Sonokawa, Ken Takashima, Yoshimi Fukushima, Takahisa Kouwaki, Hiroyuki Oshiumi
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引用次数: 0

摘要

宫颈癌主要由人类乳头瘤病毒(HPV)引起,目前已开发出多种 HPV 疫苗来预防宫颈癌的发生。疫苗包括抗原和佐剂,其中佐剂在激活先天性免疫反应以诱导适应性免疫反应方面发挥着重要作用。最近的研究表明,先天性免疫系统中存在训练有素的免疫力。然而,人们对接种人乳头瘤病毒疫苗所产生的训练有素的免疫并不十分了解。在这项研究中,我们探讨了两种 HPV 疫苗(Cervarix 和 Gardasil)引起的先天性免疫反应和训练有素的免疫力。Cervarix 包括单磷脂 A 和铝佐剂,能显著增加 RAW264.7 细胞中 IL-6 和 IFN-β mRNA 的表达。相反,仅含有铝佐剂的加卫苗几乎没有细胞因子表达,但增加了 TLRs 的表达。此外,Cervarix 能显著增加小鼠巨噬细胞中 IL-1β 的分泌,而 Gardasil 只能轻微诱导 IL-1β 的分泌。有趣的是,加德西的初始刺激增强了TLR配体二次刺激时IL-6和TNF-α mRNA的表达,这表明加德西能诱导巨噬细胞产生训练有素的免疫力。此外,给小鼠注射加德西后,血清中的 TNF-α 在继发性 TLR 刺激下产生增加。我们的研究结果表明,HPV 疫苗有能力诱导训练有素的免疫,从而调节 TLR 配体反应。
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HPV vaccines induce trained immunity and modulate pro-inflammatory cytokine expression in response to secondary Toll-like receptor stimulations

Cervical cancer is caused mostly by human papillomavirus (HPV), and several HPV vaccines have been developed to prevent its onset. Vaccines include antigens as well as adjuvants, with adjuvants playing an important role in activating the innate immune responses necessary for inducing adaptive immunological responses. Recent research has shown the presence of trained immunity inside the innate immune system. However, trained immunity conferred by HPV vaccinations is not well understood. In this work, we explored the innate immune responses and trained immunity caused by two HPV vaccines, Cervarix and Gardasil. Cervarix includes monophosphoryl lipid A and an aluminum adjuvant, and it significantly increased the expression of IL-6 and IFN-β mRNAs in RAW264.7 cells. On the contrary, Gardasil, which only includes an aluminum adjuvant, exhibited little cytokine expression but increased the expression of TLRs. Furthermore, Cervarix significantly increased IL-1β secretion from mouse macrophages, while Gardasil only mildly induced IL-1β secretion. Interestingly, initial stimulation with Gardasil enhanced the expression of IL-6 and TNF-α mRNAs upon secondary stimulation with TLR ligands, indicating that Gardasil induced trained immunity in macrophages. Moreover, Gardasil injection into mice resulted in enhanced TNF-α production in sera following secondary TLR stimulation. Our findings suggest that HPV vaccinations have the ability to induce trained immunity that modulate TLR ligand responses.

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来源期刊
Microbiology and Immunology
Microbiology and Immunology 医学-免疫学
CiteScore
5.20
自引率
3.80%
发文量
78
审稿时长
1 months
期刊介绍: Microbiology and Immunology is published in association with Japanese Society for Bacteriology, Japanese Society for Virology, and Japanese Society for Host Defense Research. It is peer-reviewed publication that provides insight into the study of microbes and the host immune, biological and physiological responses. Fields covered by Microbiology and Immunology include:Bacteriology|Virology|Immunology|pathogenic infections in human, animals and plants|pathogenicity and virulence factors such as microbial toxins and cell-surface components|factors involved in host defense, inflammation, development of vaccines|antimicrobial agents and drug resistance of microbes|genomics and proteomics.
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