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差异 miRNA 谱与疫苗免疫和衣原体感染相关的不同免疫结果相关。

Differential miRNA Profiles Correlate With Disparate Immunity Outcomes Associated With Vaccine Immunization and Chlamydial Infection.

机构信息

Department of Microbiology, Biochemistry and Immunology, Morehouse School of Medicine, Atlanta, GA, United States.

Winship Cancer Institute, Emory University School of Medicine, Atlanta, GA, United States.

出版信息

Front Immunol. 2021 Feb 22;12:625318. doi: 10.3389/fimmu.2021.625318. eCollection 2021.

DOI:10.3389/fimmu.2021.625318
PMID:33692799
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7937703/
Abstract

Vaccine-induced immune responses following immunization with promising vaccines protected experimental animals from induced upper genital tract pathologies and infertility. In contrast, primary genital infection with live does not protect against these pathologies. We hypothesized that differential miRNA profiles induced in the upper genital tracts (UGT) of mice correlate with the disparate immunity vs. pathologic outcomes associated with vaccine immunization and chlamydial infection. Thus, miRNA expression profiles in the UGT of mice after infection (Live EB) and immunization with dendritic cell (DC)-based vaccine (DC vaccine) or VCG-based vaccine (VCG vaccine) were compared using the NanoString nCounter Mouse miRNA assay. Of the 602 miRNAs differentially expressed (DE) in the UGT of immunized and infected mice, we selected 58 with counts >100 and -values < 0.05 for further analysis. Interestingly, vaccine immunization and infection induced the expression of distinct miRNA profiles with a higher proportion in vaccine-immunized compared to infected mice; DC vaccine (41), VCG vaccine (23), and Live EB (15). Hierarchical clustering analysis showed notable differences in the uniquely DE miRNAs for each experimental group, with DC vaccine showing the highest number (21 up-regulated, five down-regulated), VCG vaccine (two up-regulated, five down-regulated), and live EB (two up-regulated, four down-regulated). The DC vaccine-immunized group showed the highest number (21 up-regulated and five down-regulated compared to two up-regulated and four down-regulated in the live infected group). Pathway analysis showed that the DE miRNAs target genes that regulate several biological processes and functions associated with immune response and inflammation. These results suggest that the induction of differential miRNA expression plays a significant role in the disparate immunity outcomes associated with infection and vaccination.

摘要

疫苗接种后产生的免疫反应可预防实验动物发生诱导性上生殖道疾病和不孕。相比之下，活 初次感染并不会预防这些疾病。我们假设，在上生殖道（UGT）中诱导的差异 miRNA 谱与疫苗接种和衣原体感染相关的不同免疫与病理结果有关。因此，使用 NanoString nCounter Mouse miRNA 分析比较了小鼠感染后（活 EB）和基于树突状细胞（DC）的疫苗（DC 疫苗）或基于 VCG 的疫苗（VCG 疫苗）免疫后 UGT 中的 miRNA 表达谱。在免疫和感染的小鼠 UGT 中差异表达（DE）的 602 个 miRNA 中，我们选择了计数>100 和 -值<0.05 的 58 个 miRNA 进行进一步分析。有趣的是，疫苗免疫和 感染诱导了不同的 miRNA 表达谱，与感染小鼠相比，疫苗免疫小鼠的 miRNA 表达谱更高；DC 疫苗（41）、VCG 疫苗（23）和活 EB（15）。层次聚类分析显示，每个实验组中独特的 DE miRNAs 存在明显差异，DC 疫苗显示出最高数量（21 个上调，5 个下调），VCG 疫苗（2 个上调，5 个下调）和活 EB（2 个上调，4 个下调）。与活 感染组相比，DC 疫苗免疫组显示出更高数量的上调和下调（21 个上调和 5 个下调，而活 EB 组为 2 个上调和 4 个下调）。通路分析显示，DE miRNAs 的靶基因调节与免疫反应和炎症相关的几种生物过程和功能。这些结果表明，差异 miRNA 表达的诱导在与 感染和疫苗接种相关的不同免疫结果中起着重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/62f840972c85/fimmu-12-625318-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/e6843cd184b3/fimmu-12-625318-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/c6b1ddaf7c18/fimmu-12-625318-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/2df37264a902/fimmu-12-625318-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/4ab8fcae0d1f/fimmu-12-625318-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/1f5b9b59d1ce/fimmu-12-625318-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/62f840972c85/fimmu-12-625318-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/e6843cd184b3/fimmu-12-625318-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/c6b1ddaf7c18/fimmu-12-625318-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/2df37264a902/fimmu-12-625318-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/4ab8fcae0d1f/fimmu-12-625318-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/1f5b9b59d1ce/fimmu-12-625318-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3e92/7937703/62f840972c85/fimmu-12-625318-g0006.jpg

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