Molecular signature of aluminum hydroxide adjuvant in ovine PBMCs by integrated mRNA and microRNA transcriptome sequencing

Varela Martínez, Endika; Abendaño, Naiara; Asín, Javier; Sistiaga Poveda, Maialen; Pérez, Marta María; Reina Arias, Ramsés; Andrés Cara, Damián de; Luján, Lluís; Jugo, Begoña M.

Publication:
Molecular signature of aluminum hydroxide adjuvant in ovine PBMCs by integrated mRNA and microRNA transcriptome sequencing

dc.contributor.author	Varela Martínez, Endika
dc.contributor.author	Abendaño, Naiara
dc.contributor.author	Asín, Javier
dc.contributor.author	Sistiaga Poveda, Maialen
dc.contributor.author	Pérez, Marta María
dc.contributor.author	Reina Arias, Ramsés
dc.contributor.author	Andrés Cara, Damián de
dc.contributor.author	Luján, Lluís
dc.contributor.author	Jugo, Begoña M.
dc.contributor.department	IdAB. Instituto de Agrobiotecnología / Agrobioteknologiako Institutua	es_ES
dc.date.accessioned	2019-07-17T12:13:13Z
dc.date.available	2019-07-17T12:13:13Z
dc.date.issued	2018
dc.description.abstract	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.	en
dc.description.sponsorship	This work was supported by a MINECO project grant (AGL2013-49137-C3-3-R to BJ and AGL2013-49137-C3-2-R to LL and AGL2013-49137-C3-1 to DdA), a predoctoral fellowship from the UPV/EHU to EV-M (PIF15/361) and a postdoctoral fellowship from the UPV/EHU to NA (ESPDOC16/43).	en
dc.format.extent	16 p.
dc.format.mimetype	application/pdf	en
dc.format.mimetype	application/zip	en
dc.identifier.doi	10.3389/fimmu.2018.02406
dc.identifier.issn	1664-3224
dc.identifier.uri	https://academica-e.unavarra.es/handle/2454/33615
dc.language.iso	eng	en
dc.publisher	Frontiers Media	en
dc.relation.ispartof	Frontiers in Immunology, 9:2406	en
dc.relation.projectID	info:eu-repo/grantAgreement/MINECO//AGL2013-49137-C3-1-R/ES/	en
dc.relation.publisherversion	https://doi.org/10.3389/fimmu.2018.02406
dc.rights	© 2018 Varela-Martínez, Abendaño, Asín, Sistiaga-Poveda, Pérez, Reina, de Andrés, Luján and Jugo. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.	en
dc.rights.accessRights	info:eu-repo/semantics/openAccess
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/
dc.subject	Adjuvant	en
dc.subject	Aluminum hydroxide	en
dc.subject	MiRNA	en
dc.subject	PBMCs	en
dc.subject	RNA-seq	en
dc.subject	Sheep	en
dc.subject	Transcriptome	en
dc.subject	Vaccination	en
dc.title	Molecular signature of aluminum hydroxide adjuvant in ovine PBMCs by integrated mRNA and microRNA transcriptome sequencing	en
dc.type	info:eu-repo/semantics/article
dc.type.version	info:eu-repo/semantics/publishedVersion	en
dc.type.version	Versión publicada / Argitaratu den bertsioa	es
dspace.entity.type	Publication
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relation.isAuthorOfPublication.latestForDiscovery	5eb332ef-80cd-4c2b-942f-e48c9d3725f2