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Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages

African swine fever (ASF) poses a severe threat to the global pig industry for which currently there is no available vaccine. The aetiological ASF virus (ASFV) has a predilection for cells of the myeloid lineage, however little is known about its interaction with polarised macrophages. This study fo...

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Autores principales: Franzoni, Giulia, Razzuoli, Elisabetta, Dei Giudici, Silvia, Carta, Tania, Galleri, Grazia, Zinellu, Susanna, Ledda, Mauro, Angioi, Pierpaolo, Modesto, Paola, Graham, Simon P., Oggiano, Annalisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157553/
https://www.ncbi.nlm.nih.gov/pubmed/32178332
http://dx.doi.org/10.3390/pathogens9030209
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author Franzoni, Giulia
Razzuoli, Elisabetta
Dei Giudici, Silvia
Carta, Tania
Galleri, Grazia
Zinellu, Susanna
Ledda, Mauro
Angioi, Pierpaolo
Modesto, Paola
Graham, Simon P.
Oggiano, Annalisa
author_facet Franzoni, Giulia
Razzuoli, Elisabetta
Dei Giudici, Silvia
Carta, Tania
Galleri, Grazia
Zinellu, Susanna
Ledda, Mauro
Angioi, Pierpaolo
Modesto, Paola
Graham, Simon P.
Oggiano, Annalisa
author_sort Franzoni, Giulia
collection PubMed
description African swine fever (ASF) poses a severe threat to the global pig industry for which currently there is no available vaccine. The aetiological ASF virus (ASFV) has a predilection for cells of the myeloid lineage, however little is known about its interaction with polarised macrophages. This study focused on the in vitro interactions of porcine monocyte-derived un-activated (moMΦ), classically (moM1), alternatively (moM2), and IFN-α-activated macrophages with two genotype I ASFV strains: virulent 22653/14 and attenuated NH/P68. At a high multiplicity of infection, NH/P68, but not 22653/14, presented a reduced ability to infect moM1 and IFN−α-activated moMΦ compared to moMΦ. IFN-α activation resulted in a dose-dependent reduction in the proportion of ASFV-infected cells. Both strains replicated efficiently in all the subsets. While higher levels of IL-1α, IL-1β, and IL-18 were secreted by NH/P68-infected moM1 compared to 22653/14, both strains negatively affected moMΦ ability to release IL-6, IL-12, TNF-α in response to classical activation or stimulation with a TLR2 agonist. Our results suggest that ASFV 22653/14 covertly replicates in macrophages, compromising the development of effective immune responses. Attenuated NH/P68 has partially lost these mechanisms, which may enhance immune surveillance. A better understating of these mechanisms should aid the rational design of live attenuated ASFV vaccines.
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spelling pubmed-71575532020-05-01 Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages Franzoni, Giulia Razzuoli, Elisabetta Dei Giudici, Silvia Carta, Tania Galleri, Grazia Zinellu, Susanna Ledda, Mauro Angioi, Pierpaolo Modesto, Paola Graham, Simon P. Oggiano, Annalisa Pathogens Article African swine fever (ASF) poses a severe threat to the global pig industry for which currently there is no available vaccine. The aetiological ASF virus (ASFV) has a predilection for cells of the myeloid lineage, however little is known about its interaction with polarised macrophages. This study focused on the in vitro interactions of porcine monocyte-derived un-activated (moMΦ), classically (moM1), alternatively (moM2), and IFN-α-activated macrophages with two genotype I ASFV strains: virulent 22653/14 and attenuated NH/P68. At a high multiplicity of infection, NH/P68, but not 22653/14, presented a reduced ability to infect moM1 and IFN−α-activated moMΦ compared to moMΦ. IFN-α activation resulted in a dose-dependent reduction in the proportion of ASFV-infected cells. Both strains replicated efficiently in all the subsets. While higher levels of IL-1α, IL-1β, and IL-18 were secreted by NH/P68-infected moM1 compared to 22653/14, both strains negatively affected moMΦ ability to release IL-6, IL-12, TNF-α in response to classical activation or stimulation with a TLR2 agonist. Our results suggest that ASFV 22653/14 covertly replicates in macrophages, compromising the development of effective immune responses. Attenuated NH/P68 has partially lost these mechanisms, which may enhance immune surveillance. A better understating of these mechanisms should aid the rational design of live attenuated ASFV vaccines. MDPI 2020-03-12 /pmc/articles/PMC7157553/ /pubmed/32178332 http://dx.doi.org/10.3390/pathogens9030209 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Franzoni, Giulia
Razzuoli, Elisabetta
Dei Giudici, Silvia
Carta, Tania
Galleri, Grazia
Zinellu, Susanna
Ledda, Mauro
Angioi, Pierpaolo
Modesto, Paola
Graham, Simon P.
Oggiano, Annalisa
Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title_full Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title_fullStr Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title_full_unstemmed Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title_short Comparison of Macrophage Responses to African Swine Fever Viruses Reveals that the NH/P68 Strain is Associated with Enhanced Sensitivity to Type I IFN and Cytokine Responses from Classically Activated Macrophages
title_sort comparison of macrophage responses to african swine fever viruses reveals that the nh/p68 strain is associated with enhanced sensitivity to type i ifn and cytokine responses from classically activated macrophages
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157553/
https://www.ncbi.nlm.nih.gov/pubmed/32178332
http://dx.doi.org/10.3390/pathogens9030209
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