Cross-reactive antibodies facilitate innate sensing of dengue and Zika viruses.
Cross-reactive antibodies facilitate innate sensing of dengue and Zika viruses.
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DOI：
10.1172/jci.insight.151782
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发表时间：
2022-05
期刊：
影响因子：
8
通讯作者：
Laura K. Aisenberg;Kimberly E. Rousseau;K. Cascino;G. Massaccesi;William H. Aisenberg;Wensheng Luo;K. Muthumani;D. Weiner;S. Whitehead;M. Chattergoon;A. Durbin;Andrea L. Cox
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文献类型：
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作者：
Laura K. Aisenberg;Kimberly E. Rousseau;K. Cascino;G. Massaccesi;William H. Aisenberg;Wensheng Luo;K. Muthumani;D. Weiner;S. Whitehead;M. Chattergoon;A. Durbin;Andrea L. Cox
埃及伊蚊传播登革热病毒(DENV)和寨卡病毒(ZIKV)。流行区的个人既有感染这两种病毒的风险，也有反复感染DENV的风险。在存在抗DENV抗体的情况下，继发DENV感染的结果从轻微到危及生命不等。此外，交叉反应抗体在ZIKV感染过程中的作用尚不清楚。我们评估了DENV疫苗接种后分离的交叉反应DENV单抗或多克隆免疫球蛋白在血浆细胞样树突状细胞(PDCs)对异型DENV和ZIKV感染细胞的反应中上调I型干扰素(干扰素)产生的能力。我们发现抗体增加PDC干扰素产生的能力有一定范围，并且干扰素的产生与抗体结合受感染细胞表面的能力呈正相关。Fc受体与PDC的结合和Fab与感染细胞上表位的结合需要通过提供和促进PDC对DENV或ZIKV的感知来介导增加的干扰素产生。这代表了一种独立于中和的机制，通过这种机制，先前存在的交叉反应DENV抗体可以保护一部分人在继发性异型DENV或ZIKV感染期间免受严重后果。
The Aedes aegypti mosquito transmits both dengue (DENV) and Zika (ZIKV) viruses. Individuals in endemic areas are at risk for infection with both viruses as well as repeated DENV infection. In the presence of anti-DENV antibodies, outcomes of secondary DENV infection range from mild to life-threatening. Further, the role of cross-reactive antibodies on the course of ZIKV infection remains unclear.We assessed the ability of cross-reactive DENV monoclonal antibodies or polyclonal immunoglobulin isolated after DENV vaccination to upregulate type I interferon (IFN) production by plasmacytoid dendritic cells (pDCs) in response to both heterotypic DENV- and ZIKV- infected cells. We found a range in the ability of antibodies to increase pDC IFN production and a positive correlation between IFN production and the ability of an antibody to bind to the infected cell surface. Engagement of Fc receptors on the pDC and Fab binding of an epitope on infected cells was required to mediate increased IFN production by providing specificity to and promoting pDC sensing of DENV or ZIKV. This represents a mechanism independent of neutralization by which pre-existing cross-reactive DENV antibodies could protect a subset of individuals from severe outcomes during secondary heterotypic DENV or ZIKV infection.