Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.
Sex-associated early-life viral innate immune response is transcriptionally associated with chromatin remodeling of type-I IFN-inducible genes.
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DOI：
10.1016/j.mucimm.2023.06.002
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发表时间：
2023-10
影响因子：
8
通讯作者：
Lukacs, Nicholas W.
中科院分区：
文献类型：
--
作者：
Malinczak, Carrie-Anne;Fonseca, Wendy;Mire, Mohamed M.;Parolia, Abhijit;Chinnaiyan, Arul;Rasky, Andrew J.;Morris, Susan;Yagi, Kazuma;Bermick, Jennifer R.;Lukacs, Nicholas W.
本研究通过检测骨髓来源的树突状细胞（BMDCs）来研究性别相关的系统性先天免疫差异。与雄性BMDC相比，从7日龄小鼠中生长的BMDC在雌性中显示增强的I型干扰素（IFN）信号传导。呼吸道合胞病毒（RSV）感染7日龄小鼠后，在感染后4周，观察到BMDC的表型显着改变的性别依赖性的方式。这些改变包括来自早期RSV感染雌性小鼠的BMDC中Ifnb/白细胞介素（IL 12 a）和IFNAR 1+表达增强，导致T细胞产生IFN-γ增加。在肺致敏后证实了表型差异，其中EL-RSV雄性来源的BMDC促进增强的T辅助细胞2/17应答并在RSV感染后加重疾病，而EL-RSV/F BMDC致敏具有相对保护性。使用测序分析（ATAC-seq）进行的转座酶可接近染色质的测定表明，EL-RSV/F BMDC在I型免疫基因附近具有增强的染色质可接近性，预测JUN、STAT 1/2和IRF 1/8转录因子在可接近区域中具有结合位点。重要的是，人脐带血来源的单核细胞的ATAC-seq显示出与女性来源的单核细胞相似的性别相关染色质景观，在I型免疫基因中具有更多的可及性。这些研究增强了我们对先天免疫中性别相关差异的理解，这些差异是由女性通过I型免疫早期感染扩增的表观遗传学控制的转录程序引起的。
This study investigates sex-associated systemic innate immune differences by examining bone marrow-derived dendritic cells (BMDCs). BMDC grown from 7-day-old mice show enhanced type-I interferon (IFN) signaling in female compared to male BMDC. Upon respiratory syncytial virus (RSV) infection of 7-day-old mice, a significantly altered phenotype of BMDC at 4 weeks post-infection is observed in a sex-dependent manner. The alterations include heightened Ifnb/ interleukin (Il12a) and enhanced IFNAR1 + expression in BMDC from early-life RSV-infected female mice that leads to increased IFN-γ production by T cells. Phenotypic differences were verified upon pulmonary sensitization whereby EL-RSV male-derived BMDC promoted enhanced T helper 2/17 responses and exacerbated disease upon RSV infection while EL-RSV/F BMDC sensitization was relatively protective. Assay for transposase-accessible chromatin using sequencing analysis (ATAC-seq) demonstrated that EL-RSV/F BMDC had enhanced chromatin accessibility near type-I immune genes with JUN, STAT1/2, and IRF1/8 transcription factors predicted to have binding sites in accessible regions. Importantly, ATAC-seq of human cord blood-derived monocytes displayed a similar sex-associated chromatin landscape with female-derived monocytes having more accessibility in type-I immune genes. These studies enhance our understanding of sex-associated differences in innate immunity by epigenetically controlled transcriptional programs amplified by early-life infection in females via type-I immunity.
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影响因子：
3
作者：
Amaral ML;Erikson GA;Shokhirev MN
通讯作者：
Shokhirev MN
DOI：
10.1038/nri2394
发表时间：
2008-09
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Fish EN
通讯作者：
Fish EN
影响因子：
5.7
作者：
Bermick JR;Lambrecht NJ;denDekker AD;Kunkel SL;Lukacs NW;Hogaboam CM;Schaller MA
通讯作者：
Schaller MA
影响因子：
5.3
作者：
Falvo, JV;Parekh, BS;Maniatis, T
通讯作者：
Maniatis, T
影响因子：
13
作者：
Gabriele L;Fragale A;Romagnoli G;Parlato S;Lapenta C;Santini SM;Ozato K;Capone I
通讯作者：
Capone I