Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19.
Type I IFN-dependent antibody response at the basis of sex dimorphism in the outcome of COVID-19.
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DOI：
10.1016/j.cytogfr.2020.10.001
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发表时间：
2021-04
影响因子：
13
通讯作者：
Capone I
中科院分区：
文献类型：
--
作者：
Gabriele L;Fragale A;Romagnoli G;Parlato S;Lapenta C;Santini SM;Ozato K;Capone I
严重急性呼吸道综合征冠状病毒2型（SARS-CoV-2）是2019年冠状病毒病（COVID-19）大流行的病原体，主要在老年男性中引起严重肺炎。流行病学数据清楚地表明，疾病结果存在性别差异，尽管对感染的易感性相似，但男性约占死亡人数的70%。众所周知，女性具有更高的产生抗体的能力，这与SARS-Cov-2感染背景下的病毒清除和疾病消退相关。许多X连锁的免疫基因逃避X失活，在雌性免疫细胞中表现出双等位基因表达，特别是在浆细胞样树突状细胞（pDC）中。PDCs在雌性中更活跃，并且在与训练免疫相关的整个表观遗传机制中具有诱导IFN-α介导的B细胞活化和分化为产生抗体的浆细胞的高能力。因此，我们假设在SARS-CoV-2感染后，参与pDC介导的I型IFN（IFN-I）信号传导的X连锁基因的表观遗传修饰在女性中更有效地发生，用于诱导中和抗体应答作为驱动性别偏倚疾病结果的免疫相关物。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the ongoing coronavirus disease 2019 (COVID-19) pandemic, induces severe pneumonia mainly in elderly males. Epidemiological data clearly indicate sex-based differences in disease outcomes, with men accounting for about 70 % of deaths, despite similar susceptibility to infection. It is well known that females are endowed with higher capacity to produce antibodies, which correlates with viral clearance and disease resolution in the context of SARS-Cov-2 infection. Many X-linked immune genes escape X inactivation showing biallelic expression in female immune cells, particularly in plasmacytoid dendritic cells (pDCs). PDCs are more active in females and endowed with high capability to induce IFN-α-mediated B cell activation and differentiation into antibody-producing plasma cells throughout epigenetic mechanisms linked to trained immunity. Thus, we hypothesize that following SARS-CoV-2 infection, epigenetic modifications of X-linked genes involved in pDC-mediated type I IFN (IFN-I) signaling occurs more effectively in females, for inducing neutralizing antibody response as an immune correlate driving sex-biased disease outcome.
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DOI：
10.1126/science.abd4585
发表时间：
2020-10-23
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
Casanova JL
DOI：
10.4049/jimmunol.1501684
发表时间：
2015-12-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
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DOI：
10.1126/science.aaa1578
发表时间：
2015-04-24
期刊：
Science (New York, N.Y.)
影响因子：
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通讯作者：
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影响因子：
7.3
作者：
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通讯作者：
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影响因子：
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