Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice
Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils i...
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MDPI AG
2021-02-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/10/3/509 |
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| author | Meenakshi Tiwary Robert J. Rooney Swantje Liedmann Kim S. LeMessurier Amali E. Samarasinghe |
| author_facet | Meenakshi Tiwary Robert J. Rooney Swantje Liedmann Kim S. LeMessurier Amali E. Samarasinghe |
| author_sort | Meenakshi Tiwary |
| collection | DOAJ |
| description | Eosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza. |
| first_indexed | 2024-03-09T06:16:34Z |
| format | Article |
| id | doaj.art-60618182d8cf48bfadecbc1947cba90d |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-09T06:16:34Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-60618182d8cf48bfadecbc1947cba90d2023-12-03T11:52:20ZengMDPI AGCells2073-44092021-02-0110350910.3390/cells10030509Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 MiceMeenakshi Tiwary0Robert J. Rooney1Swantje Liedmann2Kim S. LeMessurier3Amali E. Samarasinghe4Division of Pulmonology, Allergy-Immunology and Sleep, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADivision of Pulmonology, Allergy-Immunology and Sleep, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADepartment of Immunology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USADivision of Pulmonology, Allergy-Immunology and Sleep, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USADivision of Pulmonology, Allergy-Immunology and Sleep, Department of Pediatrics, College of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USAEosinophils, previously considered terminally differentiated effector cells, have multifaceted functions in tissues. We previously found that allergic mice with eosinophil-rich inflammation were protected from severe influenza and discovered specialized antiviral effector functions for eosinophils including promoting cellular immunity during influenza. In this study, we hypothesized that eosinophil responses during the early phase of influenza contribute to host protection. Using in vitro and in vivo models, we found that eosinophils were rapidly and dynamically regulated upon influenza A virus (IAV) exposure to gain migratory capabilities to traffic to lymphoid organs after pulmonary infection. Eosinophils were capable of neutralizing virus upon contact and combinations of eosinophil granule proteins reduced virus infectivity through hemagglutinin inactivation. Bi-directional crosstalk between IAV-exposed epithelial cells and eosinophils occurred after IAV infection and cross-regulation promoted barrier responses to improve antiviral defenses in airway epithelial cells. Direct interactions between eosinophils and airway epithelial cells after IAV infection prevented virus-induced cytopathology in airway epithelial cells in vitro, and eosinophil recipient IAV-infected mice also maintained normal airway epithelial cell morphology. Our data suggest that eosinophils are important in the early phase of IAV infection providing immediate protection to the epithelial barrier until adaptive immune responses are deployed during influenza.https://www.mdpi.com/2073-4409/10/3/509adhesion moleculescell damageactivationmigration |
| spellingShingle | Meenakshi Tiwary Robert J. Rooney Swantje Liedmann Kim S. LeMessurier Amali E. Samarasinghe Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice Cells adhesion molecules cell damage activation migration |
| title | Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice |
| title_full | Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice |
| title_fullStr | Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice |
| title_full_unstemmed | Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice |
| title_short | Eosinophil Responses at the Airway Epithelial Barrier during the Early Phase of Influenza a Virus Infection in C57BL/6 Mice |
| title_sort | eosinophil responses at the airway epithelial barrier during the early phase of influenza a virus infection in c57bl 6 mice |
| topic | adhesion molecules cell damage activation migration |
| url | https://www.mdpi.com/2073-4409/10/3/509 |
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