Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)

In recent years, the innate immune response has gained importance since evidence indicates that after an adequate priming protocol, it is possible to obtain some prolonged and enhanced immune responses. Nevertheless, several factors, such as the timing and method of administration of the immunostimu...

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Main Authors: Margarita Álvarez-Rodríguez, Patricia Pereiro, Felipe E. Reyes-López, Lluis Tort, Antonio Figueras, Beatriz Novoa
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-07-01
Series:Frontiers in Immunology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fimmu.2018.01575/full
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author Margarita Álvarez-Rodríguez
Patricia Pereiro
Felipe E. Reyes-López
Lluis Tort
Antonio Figueras
Beatriz Novoa
author_facet Margarita Álvarez-Rodríguez
Patricia Pereiro
Felipe E. Reyes-López
Lluis Tort
Antonio Figueras
Beatriz Novoa
author_sort Margarita Álvarez-Rodríguez
collection DOAJ
description In recent years, the innate immune response has gained importance since evidence indicates that after an adequate priming protocol, it is possible to obtain some prolonged and enhanced immune responses. Nevertheless, several factors, such as the timing and method of administration of the immunostimulants, must be carefully considered. An inappropriate protocol can transform the treatments into a double-edged sword for the teleost immune system, resulting in a stressful and immunosuppressive state. In this work, we analyzed the long-term effects of different stimuli (β-glucans, lipopolysaccharide, and polyinosinic:polycytidylic acid) on the transcriptome modulation induced by Spring Viremia Carp Virus (SVCV) in adult zebrafish (Danio rerio) and on the mortality caused by this infection. At 35 days post-immunostimulation, the transcriptome was found to be highly altered compared to that of the control fish, and these stimuli also conditioned the response to SVCV challenge, especially in the case of β-glucans. No protection against SVCV was found with any of the stimuli, and non-significant higher mortalities were even observed, especially with β-glucans. However, in the short term (pre-stimulation with β-glucan and infection after 7 days), slight protection was observed after infection. The transcriptome response in the zebrafish kidney at 35 days posttreatment with β-glucans revealed a significant response associated with stress and immunosuppression. The identification of genes that were differentially expressed before and after the infection seemed to indicate a high energy cost of the immunostimulation that was prolonged over time and could explain the lack of protection against SVCV. Differential responses to stress and alterations in lipid metabolism, the tryptophan–kynurenine pathway, and interferon-gamma signaling seem to be some of the mechanisms involved in this response, which represents the end of trained immunity and the beginning of a stressful state characterized by immunosuppression.
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spelling doaj.art-ba3f1fefd861445f9eab4e8c08bfbaed2022-12-22T03:22:43ZengFrontiers Media S.A.Frontiers in Immunology1664-32242018-07-01910.3389/fimmu.2018.01575388727Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)Margarita Álvarez-Rodríguez0Patricia Pereiro1Felipe E. Reyes-López2Lluis Tort3Antonio Figueras4Beatriz Novoa5Institute of Marine Research (IIM), National Research Council (CSIC), Vigo, SpainInstitute of Marine Research (IIM), National Research Council (CSIC), Vigo, SpainDepartment of Cell Biology, Physiology and Immunology, Universidad Autónoma de Barcelona, Bellaterra, SpainDepartment of Cell Biology, Physiology and Immunology, Universidad Autónoma de Barcelona, Bellaterra, SpainInstitute of Marine Research (IIM), National Research Council (CSIC), Vigo, SpainInstitute of Marine Research (IIM), National Research Council (CSIC), Vigo, SpainIn recent years, the innate immune response has gained importance since evidence indicates that after an adequate priming protocol, it is possible to obtain some prolonged and enhanced immune responses. Nevertheless, several factors, such as the timing and method of administration of the immunostimulants, must be carefully considered. An inappropriate protocol can transform the treatments into a double-edged sword for the teleost immune system, resulting in a stressful and immunosuppressive state. In this work, we analyzed the long-term effects of different stimuli (β-glucans, lipopolysaccharide, and polyinosinic:polycytidylic acid) on the transcriptome modulation induced by Spring Viremia Carp Virus (SVCV) in adult zebrafish (Danio rerio) and on the mortality caused by this infection. At 35 days post-immunostimulation, the transcriptome was found to be highly altered compared to that of the control fish, and these stimuli also conditioned the response to SVCV challenge, especially in the case of β-glucans. No protection against SVCV was found with any of the stimuli, and non-significant higher mortalities were even observed, especially with β-glucans. However, in the short term (pre-stimulation with β-glucan and infection after 7 days), slight protection was observed after infection. The transcriptome response in the zebrafish kidney at 35 days posttreatment with β-glucans revealed a significant response associated with stress and immunosuppression. The identification of genes that were differentially expressed before and after the infection seemed to indicate a high energy cost of the immunostimulation that was prolonged over time and could explain the lack of protection against SVCV. Differential responses to stress and alterations in lipid metabolism, the tryptophan–kynurenine pathway, and interferon-gamma signaling seem to be some of the mechanisms involved in this response, which represents the end of trained immunity and the beginning of a stressful state characterized by immunosuppression.https://www.frontiersin.org/article/10.3389/fimmu.2018.01575/fullzebrafishimmunostimulantsβ-glucansstresstoleranceIFN-γ
spellingShingle Margarita Álvarez-Rodríguez
Patricia Pereiro
Felipe E. Reyes-López
Lluis Tort
Antonio Figueras
Beatriz Novoa
Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
Frontiers in Immunology
zebrafish
immunostimulants
β-glucans
stress
tolerance
IFN-γ
title Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
title_full Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
title_fullStr Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
title_full_unstemmed Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
title_short Analysis of the Long-Lived Responses Induced by Immunostimulants and Their Effects on a Viral Infection in Zebrafish (Danio rerio)
title_sort analysis of the long lived responses induced by immunostimulants and their effects on a viral infection in zebrafish danio rerio
topic zebrafish
immunostimulants
β-glucans
stress
tolerance
IFN-γ
url https://www.frontiersin.org/article/10.3389/fimmu.2018.01575/full
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