锰打破了HBs-Ag的免疫耐受性

StephenW

Manganese Breaks the Immune Tolerance of HBs-Ag
Mengxin Lin  1 , Ruyi Guo  1 , Cuiping Ma  1 , Dawu Zeng  2 , Zhijun Su  1
Affiliations
Affiliations

    1
    Department of Infectious Disease, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China.
    2
    Liver Research Center, the First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China.

    PMID: 33614817 PMCID: PMC7885859 DOI: 10.1093/ofid/ofab028

Abstract

Background: Manganese (Mn2+) has been shown to promote type I interferon (IFN) production and activate the cyclic GMP-AMP synthase (cGAS)/Stimulator of Interferon Genes (STING) signaling pathway, suggesting that Mn2+ could be used as an adjuvant for vaccination.

Methods: In present study, the effects of Mn2+ on vaccination against hepatitis B virus (HBV) were evaluated. We treated mouse hepatocytes and kuppfer cells with Mn2+ with or without adeno-associated virus (AAV)-HBV infection. Expression of IFN-α and IFN-β and activation of TBK1 and IRF3 were monitored. Wild-type and STING-/- mice were treated with Mn2+ and then infected with AAV-HBV. Serum levels of HBV surface antigen (HBsAg), alanine aminotransferase (ALT) activity, IFN-α, and IFN-β were detected. Lymphocyte infiltration in the liver was evaluated. HBsAg-Tg mice were vaccinated with Mn2+ and HBsAg. The serum levels of HBsAg antibody, alanine transaminase activity, and IFN-β were monitored after vaccination.

Results: Mn2+ promoted IFN-α and IFN-β production in mouse hepatocytes and kuppfer cells. Mn2+ failed to promote IFN-α and IFN-β production in kuppfer cells deficient in STING. Mn2+ promoted activation/phosphorylation of TBK1 and IRF3 during AAV-HBV infection. Mn2+ decreased serum levels of HBsAG, increased serum levels of alanine aminotransferase (ALT), IFN-α and IFN-β, and enhanced lymphocyte infiltration and the percentage of IFN-γ-producing CD8+ T cells in the liver of AAV-HBV-infected mice. In contrast, Mn2+ treatment did not affect serum levels of HBsAG, ALT, IFN-α, or IFN-β in STING-deficient mice.

Conclusions: Mn2 + promoted HBsAG antibody, ALT, and IFN-β production after HBsAG immunization. Mn2+ promoted type I IFN production in AAV-HBV infection and HBsAG immunization and could be used as an adjuvant for vaccination.

Keywords: HBV; manganese; type I IFN; vaccine.

© The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

StephenW

锰打破了HBs-Ag的免疫耐受性
林梦欣1，郭如意1，马翠萍1，曾大悟2，苏志军1
隶属关系
隶属关系

    1个
    福建医科大学附属泉州第一医院传染病科，福建泉州。
    2
    福建医科大学附属第一医院肝病研究中心，福建福州。

    PMID：33614817 PMCID：PMC7885859 DOI：10.1093 / ofid / ofab028

抽象的

背景：锰（Mn2 +）已显示出能促进I型干扰素（IFN）的产生并激活环状GMP-AMP合酶（cGAS）/干扰素基因刺激物（STING）信号传导途径，表明Mn2 +可用作佐剂。疫苗接种。

方法：在本研究中，评估了Mn2 +对乙型肝炎病毒（HBV）疫苗接种的影响。我们用Mn2 +处理小鼠肝细胞和kuppfer细胞，并伴或不伴有腺相关病毒（AAV）-HBV感染。监测IFN-α和IFN-β的表达以及TBK1和IRF3的激活。用Mn2 +处理野生型和STING-/-小鼠，然后用AAV-HBV感染。检测血清的HBV表面抗原（HBsAg），丙氨酸转氨酶（ALT）活性，IFN-α和IFN-β。评价肝中的淋巴细胞浸润。 HBsAg-Tg小鼠接种了Mn2 +和HBsAg。疫苗接种后监测血清HBsAg抗体水平，丙氨酸转氨酶活性和IFN-β。

结果：Mn2 +促进了小鼠肝细胞和kuppfer细胞中IFN-α和IFN-β的产生。 Mn2 +不能促进STING缺失的kuppfer细胞中IFN-α和IFN-β的产生。在AAV-HBV感染过程中，Mn2 +促进TBK1和IRF3的激活/磷酸化。 Mn2 +降低了HBsAG的血清水平，提高了丙氨酸转氨酶（ALT），IFN-α和IFN-β的血清水平，并增强了AAV-HBV感染肝脏中淋巴细胞的浸润和产生IFN-γ的CD8 + T细胞的百分比老鼠。相比之下，Mn2 +处理并未影响STING缺陷小鼠的血清HBsAG，ALT，IFN-α或IFN-β。

结论：Mn2 +促进了HBsAG免疫后HBsAG抗体，ALT和IFN-β的产生。 Mn2 +促进了AAV-HBV感染和HBsAG免疫中的I型IFN产生，可用作疫苗接种的佐剂。

关键字：HBV；锰; I型IFN；疫苗。

©作者2021。由牛津大学出版社代表美国传染病学会出版。

StephenW

https://academic.oup.com/ofid/article/8/2/ofab028/6108153