Type I and Type III Interferons Differ in Their Adjuvant Activities for Influenza Vaccines
Type I and Type III Interferons Differ in Their Adjuvant Activities for Influenza Vaccines
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I 型和 III 型干扰素对流感疫苗的佐剂活性不同
DOI：
10.1128/jvi.01262-19
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发表时间：
2019
影响因子：
5.4
通讯作者：
P. Staeheli
中科院分区：
文献类型：
--
作者：
Ohnemus;Hartmann;P. Staeheli
I型和III型干扰素（IFN）可以促进小鼠的适应性免疫应答，并提高疫苗诱导的对病毒感染的抵抗力。III型IFN（IFN-λ）的佐剂效应通过间接机制特异性地增强粘膜免疫，该间接机制涉及IFN-λ诱导的胸腺基质淋巴细胞生成素（TSLP）（一种激活免疫细胞的细胞因子）的产生。迄今为止，尚不清楚先前描述的I型IFN（IFN-α/β）的佐剂作用是否也取决于TSLP以及I型IFN是否刺激不同的抗体亚型。在这里，我们表明，感染减毒活流感病毒后，缺乏功能性I型IFN受体的小鼠未能产生正常量的病毒特异性IgG 2c和伊加抗体。相反，缺乏功能性IFN-λ受体的小鼠含有正常水平的病毒特异性IgG 2c，但IgG 1和伊加抗体水平降低。当与蛋白抗原一起应用时，IFN-α刺激抗原特异性伊加和IgG 2c的产生的程度大于IgG 1，无论小鼠是否表达功能性TSLP受体，也无论疫苗是通过鼻内还是腹腔内途径应用。综上所述，这些结果表明，I型和III型干扰素的佐剂活性是不同的mechanismically。重要的是干扰素可以塑造抗病毒免疫反应，但它不是很好地理解他们如何影响疫苗的效力。我们发现，I型IFN优先促进抗原特异性IgG 2c和伊加抗体的生产后，感染减毒活流感病毒或流感亚单位疫苗免疫接种。相反，III型IFN特异性地增强流感病毒特异性IgG 1和伊加的产生。I型IFN的佐剂效应不依赖于TSLP，TSLP是III型IFN的佐剂效应所必需的。I型IFN通过鼻内或腹膜内途径增强免疫后疫苗诱导的抗体产生，而III型IFN仅在疫苗通过粘膜途径递送时才表现出其佐剂活性。我们的研究结果表明，I型和III型干扰素触发不同的途径，以提高疫苗的效力。这些知识可能被用来设计更有效的疫苗来对抗传染病。
Type I and type III interferons (IFNs) can promote adaptive immune responses in mice and improve vaccine-induced resistance to viral infections. The adjuvant effect of type III IFN (IFN-λ) specifically boosts mucosal immunity by an indirect mechanism, involving IFN-λ-induced production of thymic stromal lymphopoietin (TSLP), a cytokine that activates immune cells. To date, it remained unclear whether the previously described adjuvant effect of type I IFN (IFN-α/β) would also depend on TSLP and whether type I IFN stimulates different antibody subtypes. Here, we show that after infection with a live attenuated influenza virus, mice lacking functional type I IFN receptors failed to produce normal amounts of virus-specific IgG2c and IgA antibodies. In contrast, mice lacking functional IFN-λ receptors contained normal levels of virus-specific IgG2c but had reduced IgG1 and IgA antibody levels. When applied together with protein antigen, IFN-α stimulated the production of antigen-specific IgA and IgG2c to a greater extent than IgG1, irrespective of whether the mice expressed functional TSLP receptors and irrespective of whether the vaccine was applied by the intranasal or the intraperitoneal route. Taken together, these results demonstrate that the adjuvant activities of type I and type III IFNs are mechanistically distinct.IMPORTANCEInterferons can shape antiviral immune responses, but it is not well understood how they influence vaccine efficacy. We find that type I IFN preferentially promotes the production of antigen-specific IgG2c and IgA antibodies after infection with a live attenuated influenza virus or after immunization with influenza subunit vaccines. In contrast, type III IFN specifically enhances influenza virus-specific IgG1 and IgA production. The adjuvant effect of type I IFN was not dependent on TSLP, which is essential for the adjuvant effect of type III IFN. Type I IFN boosted vaccine-induced antibody production after immunization by the intranasal or the intraperitoneal route, whereas type III IFN exhibited its adjuvant activity only when the vaccine was delivered by the mucosal route. Our findings demonstrate that type I and type III IFNs trigger distinct pathways to enhance the efficacy of vaccines. This knowledge might be used to design more efficient vaccines against infectious diseases.
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