Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection.
Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-) inflammatory monocytes, and not neutrophils, are th...
| Main Authors: | , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
2012
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| _version_ | 1797068358973128704 |
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| author | Kok, W Denney, L Benam, K Cole, S Clelland, C Mcmichael, A Ho, L |
| author_facet | Kok, W Denney, L Benam, K Cole, S Clelland, C Mcmichael, A Ho, L |
| author_sort | Kok, W |
| collection | OXFORD |
| description | Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-) inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18(-/-) mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology. |
| first_indexed | 2024-03-06T22:09:37Z |
| format | Journal article |
| id | oxford-uuid:515c4e35-197b-494f-8f15-1feb90349a26 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T22:09:37Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:515c4e35-197b-494f-8f15-1feb90349a262022-03-26T16:19:04ZPivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:515c4e35-197b-494f-8f15-1feb90349a26EnglishSymplectic Elements at Oxford2012Kok, WDenney, LBenam, KCole, SClelland, CMcmichael, AHo, LLittle is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-) inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18(-/-) mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology. |
| spellingShingle | Kok, W Denney, L Benam, K Cole, S Clelland, C Mcmichael, A Ho, L Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title | Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title_full | Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title_fullStr | Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title_full_unstemmed | Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title_short | Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune-pathology during severe influenza A virus infection. |
| title_sort | pivotal advance invariant nkt cells reduce accumulation of inflammatory monocytes in the lungs and decrease immune pathology during severe influenza a virus infection |
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