Academic Journal

Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing

التفاصيل البيبلوغرافية
العنوان: Molecular Signature of Aluminum Hydroxide Adjuvant in Ovine PBMCs by Integrated mRNA and microRNA Transcriptome Sequencing
المؤلفون: Endika Varela-Martínez, Naiara Abendaño, Javier Asín, Maialen Sistiaga-Poveda, Marta Maria Pérez, Ramsés Reina, Damián de Andrés, Lluís Luján, Begoña M. Jugo
المصدر: Frontiers in Immunology, Vol 9 (2018)
بيانات النشر: Frontiers Media S.A., 2018.
سنة النشر: 2018
المجموعة: LCC:Immunologic diseases. Allergy
مصطلحات موضوعية: adjuvant, aluminum hydroxide, vaccination, transcriptome, miRNA, RNA-seq, Immunologic diseases. Allergy, RC581-607
الوصف: There have been few in vivo studies on the effect of aluminum hydroxide adjuvant and its influence on the immune response to vaccination. In this study, lambs received a parallel subcutaneous treatment with either commercial vaccines containing aluminum hydroxide or an equivalent dose of this compound only with the aim of identifying the activated molecular signature. Blood samples were taken from each animal at the beginning and at the end of the experiment and PBMCs isolated. Total RNA and miRNA libraries were prepared and sequenced. After alignment to the Oar3.1 reference genome and differential expression with 3 programs, gene enrichment modeling was performed. For miRNAs, miRBase and RNAcentral databases were used for detection and characterization. Three expression comparisons were made: vaccinated animals at the beginning and at the end of the treatment, adjuvanted animals at the same times, and animals of both treatments at the end of the experiment. After exposure to both treatments, a total of 2,473; 2,980 and 429 differentially expressed genes were identified in vaccinated animals, adjuvanted animals and animals at the end of both treatments, respectively. In both adjuvant and vaccine treated animals the NF-κB signaling pathway was enriched. On the other hand, it can be observed a downregulation of cytokines and cytokine receptors in the adjuvanted group compared to the vaccinated group at the final time, suggesting a milder induction of the immune response when the adjuvant is alone. As for the miRNA analysis, 95 miRNAs were detected: 64 previously annotated in Ovis aries, 11 annotated in Bos taurus and 20 newly described. Interestingly, 6 miRNAs were differentially expressed in adjuvant treated animals, and 3 and 1 in the other two comparisons. Lastly, an integrated miRNA-mRNA expression profile was developed, in which a miRNA-mediated regulation of genes related to DNA damage stimulus was observed. In brief, it seems that aluminum-containing adjuvants are not simple delivery vehicles for antigens, but also induce endogenous danger signals that can stimulate the immune system. Whether this contributes to long-lasting immune activation or to the overstimulation of the immune system remains to be elucidated.
نوع الوثيقة: article
وصف الملف: electronic resource
اللغة: English
تدمد: 1664-3224
Relation: https://www.frontiersin.org/article/10.3389/fimmu.2018.02406/full; https://doaj.org/toc/1664-3224
DOI: 10.3389/fimmu.2018.02406
URL الوصول: https://doaj.org/article/814716c1278c454e9685d3c7b5c3161b
رقم الانضمام: edsdoj.814716c1278c454e9685d3c7b5c3161b
قاعدة البيانات: Directory of Open Access Journals
الوصف
تدمد:16643224
DOI:10.3389/fimmu.2018.02406