Maternal HIV status skews transcriptomic response in infant cord blood monocytes exposed to Bacillus Calmette--Guerín.
Maternal HIV status skews transcriptomic response in infant cord blood monocytes exposed to Bacillus Calmette--Guerín.
复制标题
DOI：
10.1097/qad.0000000000002706
复制
发表时间：
2021-01-01
期刊：
影响因子：
--
通讯作者：
Wood MP
中科院分区：
文献类型：
--
作者：
Jones CI;Rose SL;Shutt A;Cairo C;Bourgeois NM;Charurat M;Sodora DL;Wood MP
与未接触艾滋病毒的婴儿相比，接触艾滋病毒的未感染婴儿表现出疫苗反应的改变和死亡率的增加。在此，评估了卡介苗（BCG）治疗后HEU和HU脐带血单核细胞（CBM）中的疫苗应答。先天反应，在体外卡介苗治疗进行了评估，通过转录分析使用从尼日利亚队列的艾滋病毒感染和未感染的妇女的CBM。HU（n=9）和HEU（n=10）婴儿CBM用BCG处理，并用Nanostring nCounter平台进行转录分析。进行差异表达和途径富集分析，并鉴定具有增强或减弱的BCG应答的转录物。BCG刺激后，与炎症基因表达相关的几种途径上调，而与HIV暴露状态无关。HU和HEU单核细胞均增加了先天性BCG应答特征性的几种细胞因子的表达，包括IL 1 β、TNFα和IL 6。使用差异表达分析，我们鉴定了与HU单核细胞相比在HEU中显著上调的基因，包括单核细胞趋化因子CCL7和抗炎细胞因子TNFAIP6。相比之下，与HEU单核细胞相比，HU中显著上调的基因包括趋化因子CCL3和细胞因子IL23A，两者都影响抗分枝杆菌T细胞应答。最后，调节前列腺素产生的两个基因CSF 2和PTGS 2在HU脐带血中也更显著地上调，表明炎性介质在HEU婴儿中受到抑制。HEU单核细胞表现出几种关键先天免疫应答的诱导改变，提供了对先天应答途径失调的机制见解，这些途径可以在治疗上靶向改善HEU婴儿的疫苗应答。
HIV-exposed uninfected (HEU) infants exhibit altered vaccine responses and an increased mortality compared to HIV-unexposed (HU) infants. Here, vaccine responses in HEU and HU cord blood monocytes (CBMs) were assessed following Bacillus Calmette-Guerín (BCG) treatment. Innate responses to in vitro BCG treatment were assessed through transcriptional profiling using CBMs obtained from a Nigerian cohort of HIV-infected and uninfected women. HU (n=9) and HEU (n=10) infant CBMs were treated with BCG and transcriptionally profiled with the Nanostring nCounter platform. Differential expression and pathway enrichment analyses were performed, and transcripts were identified with enhanced or dampened BCG responses. Following BCG stimulation, several pathways associated with inflammatory gene expression were upregulated irrespective of HIV exposure status. Both HU and HEU monocytes increased expression of several cytokines characteristic of innate BCG responses, including IL1β, TNFα, and IL6. Using differential expression analysis, we identified genes significantly upregulated in HEU compared to HU monocytes including monocyte chemokine CCL7 and anti-inflammatory cytokine TNFAIP6. In contrast, genes significantly upregulated in HU compared to HEU monocytes include chemokine CCL3 and cytokine IL23A, both of which influence anti-mycobacterial T cell responses. Finally, two genes which regulate prostaglandin production, CSF2 and PTGS2, were also more significantly upregulated in the HU cord blood indicating that inflammatory mediators are suppressed in the HEU infants. HEU monocytes exhibit altered induction of several key innate immune responses, providing mechanistic insights into dysregulated innate response pathways that can be therapeutically targeted to improve vaccine responses in HEU infants.