Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein
Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-08-01
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| Series: | Frontiers in Cellular and Infection Microbiology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fcimb.2020.00430/full |
| _version_ | 1818323307954438144 |
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| author | Farides Saavedra Jose L. Garrido Jose L. Garrido Francisco Fuentes-Villalobos Mario Calvo Raúl Riquelme María Luisa Rioseco Carolina Chahín Leonila Ferreira Raymond Alvarez Estefania Nova-Lamperti Maria Ines Barria |
| author_facet | Farides Saavedra Jose L. Garrido Jose L. Garrido Francisco Fuentes-Villalobos Mario Calvo Raúl Riquelme María Luisa Rioseco Carolina Chahín Leonila Ferreira Raymond Alvarez Estefania Nova-Lamperti Maria Ines Barria |
| author_sort | Farides Saavedra |
| collection | DOAJ |
| description | Hantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection. |
| first_indexed | 2024-12-13T11:10:37Z |
| format | Article |
| id | doaj.art-50b359cc30c944a69b2938341f5773af |
| institution | Directory Open Access Journal |
| issn | 2235-2988 |
| language | English |
| last_indexed | 2024-12-13T11:10:37Z |
| publishDate | 2020-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular and Infection Microbiology |
| spelling | doaj.art-50b359cc30c944a69b2938341f5773af2022-12-21T23:48:47ZengFrontiers Media S.A.Frontiers in Cellular and Infection Microbiology2235-29882020-08-011010.3389/fcimb.2020.00430546013Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus GlycoproteinFarides Saavedra0Jose L. Garrido1Jose L. Garrido2Francisco Fuentes-Villalobos3Mario Calvo4Raúl Riquelme5María Luisa Rioseco6Carolina Chahín7Leonila Ferreira8Raymond Alvarez9Estefania Nova-Lamperti10Maria Ines Barria11Department of Microbiology, Faculty of Biological Science, Biotechnology Center, Universidad de Concepción, Concepción, ChileDepartment of Microbiology, Faculty of Biological Science, Biotechnology Center, Universidad de Concepción, Concepción, ChileIchor Biologics LLC, New York, NY, United StatesDepartment of Microbiology, Faculty of Biological Science, Biotechnology Center, Universidad de Concepción, Concepción, ChileInstitute of Medicine, Universidad Austral de Chile, Valdivia, ChileHospital Puerto Montt Dr. Eduardo Schoütz Schroeder, Puerto Montt, ChileHospital Puerto Montt Dr. Eduardo Schoütz Schroeder, Puerto Montt, ChileHospital Regional Temuco Dr. Hernán Henríquez Aravena, Temuco, ChileHospital Clínico Regional Guillermo Grant Benavente, Concepción, ChileIchor Biologics LLC, New York, NY, United StatesDepartment of Clinical Biochemistry and Immunology, Faculty of Pharmacy, Universidad de Concepción, Concepción, ChileDepartment of Microbiology, Faculty of Biological Science, Biotechnology Center, Universidad de Concepción, Concepción, ChileHantavirus cardiopulmonary syndrome (HCPS) caused by Andes orthohantavirus (ANDV) in South America is a public health threat due to the significant rate of mortality and the lack of a specific treatment. Interestingly, the virus does not produce cytopathic effect, thereby the strong antiviral immune response is suspected to contribute to pathogenesis, hence is important to understand the balance between protective and harmfully immunity. CD4+ T regulatory cells (Treg) are essential to control an exacerbated immune response. In human ANDV infection, little is known about CD4+ Treg cells, which may be involved in control immunopathology associated to the infection. In this report, we characterize the phenotype of memory CD4+ Tregs in a HCPS survivor's cohort. Based on the expression of CXCR3, CCR4, and CCR6, we identified different Th-like Treg populations in ANDV survival's PBMCs. In addition, the effect of ANDV-glycoprotein virus like particles (VLP) was determined. We demonstrated that memory CD4+ Treg from HCPS present a specific phenotype, showing higher frequency of PD-1 compared to healthy donors (HD). In addition, it was observed a decrease in the frequency of Th1-like memory CD4+ Treg in HCPS, important to highlight that this signature could be preserved even years after resolution of infection. Moreover, to gain insight in the mechanism involved, we evaluated whether ANDV-glycoprotein (GP) VLP could modulate CD4+ Treg. Interestingly, ANDV-GP VLP induced a decrease in the frequency of CXCR3 (Th1-like) and an increase in CCR4 (Th2-like) memory CD4+ Treg in both HD and HCPS PBMCs, indicating that ANDV-GP could specifically act over CXCR3 and CCR4 in CD4+ Treg. This report contributes to the study of human CD4+ Treg cells in ANDV infection.https://www.frontiersin.org/article/10.3389/fcimb.2020.00430/fullCD4 TregANDV-GPVLPsHCPSTh-like TregCXCR3 |
| spellingShingle | Farides Saavedra Jose L. Garrido Jose L. Garrido Francisco Fuentes-Villalobos Mario Calvo Raúl Riquelme María Luisa Rioseco Carolina Chahín Leonila Ferreira Raymond Alvarez Estefania Nova-Lamperti Maria Ines Barria Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein Frontiers in Cellular and Infection Microbiology CD4 Treg ANDV-GP VLPs HCPS Th-like Treg CXCR3 |
| title | Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein |
| title_full | Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein |
| title_fullStr | Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein |
| title_full_unstemmed | Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein |
| title_short | Differential CD4 T Regulatory Cell Phenotype Induced by Andes Hantavirus Glycoprotein |
| title_sort | differential cd4 t regulatory cell phenotype induced by andes hantavirus glycoprotein |
| topic | CD4 Treg ANDV-GP VLPs HCPS Th-like Treg CXCR3 |
| url | https://www.frontiersin.org/article/10.3389/fcimb.2020.00430/full |
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