Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity
The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathoge...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2019-10-01
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| Series: | Frontiers in Immunology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fimmu.2019.02499/full |
| _version_ | 1818291522265677824 |
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| author | María F. Ferrer Pablo Thomas Aída O. López Ortiz Aída O. López Ortiz Andrea E. Errasti Nancy Charo Victor Romanowski Victor Romanowski Juan Gorgojo María E. Rodriguez Eugenio A. Carrera Silva Ricardo M. Gómez Ricardo M. Gómez |
| author_facet | María F. Ferrer Pablo Thomas Aída O. López Ortiz Aída O. López Ortiz Andrea E. Errasti Nancy Charo Victor Romanowski Victor Romanowski Juan Gorgojo María E. Rodriguez Eugenio A. Carrera Silva Ricardo M. Gómez Ricardo M. Gómez |
| author_sort | María F. Ferrer |
| collection | DOAJ |
| description | The New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies. |
| first_indexed | 2024-12-13T02:45:24Z |
| format | Article |
| id | doaj.art-655665295645498a83f1b259f0f0b417 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T02:45:24Z |
| publishDate | 2019-10-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-655665295645498a83f1b259f0f0b4172022-12-22T00:02:12ZengFrontiers Media S.A.Frontiers in Immunology1664-32242019-10-011010.3389/fimmu.2019.02499475243Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain PathogenicityMaría F. Ferrer0Pablo Thomas1Aída O. López Ortiz2Aída O. López Ortiz3Andrea E. Errasti4Nancy Charo5Victor Romanowski6Victor Romanowski7Juan Gorgojo8María E. Rodriguez9Eugenio A. Carrera Silva10Ricardo M. Gómez11Ricardo M. Gómez12Laboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaLaboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaLaboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaLaboratorio de Trombosis Experimental, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, ArgentinaFacultad de Medicina, Instituto de Farmacologia, University of Buenos Aries, Buenos Aires, ArgentinaLaboratorio de Trombosis Experimental, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, ArgentinaLaboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaGlobal Viral Network, Baltimore, MD, United StatesCentro de Investigación y Desarrollo en Fermentaciones Industriales, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaCentro de Investigación y Desarrollo en Fermentaciones Industriales, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaLaboratorio de Trombosis Experimental, Instituto de Medicina Experimental, CONICET-Academia Nacional de Medicina, Buenos Aires, ArgentinaLaboratorio de Virus Animales, Instituto de Biotecnología y Biología Molecular, CONICET-Universidad Nacional de La Plata, La Plata, ArgentinaGlobal Viral Network, Baltimore, MD, United StatesThe New World arenavirus Junin (JUNV) is the etiological agent of Argentine hemorrhagic fever (AHF). Previous studies of human macrophage infection by the Old-World arenaviruses Mopeia and Lassa showed that while the non-pathogenic Mopeia virus replicates and activates human macrophages, the pathogenic Lassa virus replicates but fails to activate human macrophages. Less is known in regard to the impact of New World arenavirus infection on the human macrophage immune response. Macrophage activation is critical for controlling infections but could also be usurped favoring immune evasion. Therefore, it is crucial to understand how the JUNV infection modulates macrophage plasticity to clarify its role in AHF pathogenesis. With this aim in mind, we compared infection with the attenuated Candid 1 (C#1) or the pathogenic P strains of the JUNV virus in human macrophage cultures. The results showed that both JUNV strains similarly replicated and induced morphological changes as early as 1 day post-infection. However, both strains differentially induced the expression of CD71, the receptor for cell entry, the activation and maturation molecules CD80, CD86, and HLA-DR and selectively modulated cytokine production. Higher levels of TNF-α, IL-10, and IL-12 were detected with C#1 strain, while the P strain induced only higher levels of IL-6. We also found that C#1 strain infection skewed macrophage polarization to M1, whereas the P strain shifted the response to an M2 phenotype. Interestingly, the MERTK receptor, that negatively regulates the immune response, was down-regulated by C#1 strain and up-regulated by P strain infection. Similarly, the target genes of MERTK activation, the cytokine suppressors SOCS1 and SOCS3, were also increased after P strain infection, in addition to IRF-1, that regulates type I IFN levels, which were higher with C#1 compared with P strain infection. Together, this differential activation/polarization pattern of macrophages elicited by P strain suggests a more evasive immune response and may have important implications in the pathogenesis of AHF and underpinning the development of new potential therapeutic strategies.https://www.frontiersin.org/article/10.3389/fimmu.2019.02499/fulljunin virushuman macrophagesTAM receptorsmacrophage activationmacrophage polarizationIFN-I |
| spellingShingle | María F. Ferrer Pablo Thomas Aída O. López Ortiz Aída O. López Ortiz Andrea E. Errasti Nancy Charo Victor Romanowski Victor Romanowski Juan Gorgojo María E. Rodriguez Eugenio A. Carrera Silva Ricardo M. Gómez Ricardo M. Gómez Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity Frontiers in Immunology junin virus human macrophages TAM receptors macrophage activation macrophage polarization IFN-I |
| title | Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity |
| title_full | Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity |
| title_fullStr | Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity |
| title_full_unstemmed | Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity |
| title_short | Junin Virus Triggers Macrophage Activation and Modulates Polarization According to Viral Strain Pathogenicity |
| title_sort | junin virus triggers macrophage activation and modulates polarization according to viral strain pathogenicity |
| topic | junin virus human macrophages TAM receptors macrophage activation macrophage polarization IFN-I |
| url | https://www.frontiersin.org/article/10.3389/fimmu.2019.02499/full |
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