Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses.
Mitochondrial antiviral signaling protein (MAVS) is a critical innate immune signaling protein that directs the actions of the RIG-I-like receptor (RLR) signaling pathway of RNA virus recognition and initiation of anti-viral immunity against West Nile virus (WNV). In the absence of MAVS, mice die mo...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2019-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0218928 |
| _version_ | 1818590861636665344 |
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| author | Kelsey Roe Daniela Giordano Lucy B Young Kevin E Draves Ursula Holder Mehul S Suthar Michael Gale Edward A Clark |
| author_facet | Kelsey Roe Daniela Giordano Lucy B Young Kevin E Draves Ursula Holder Mehul S Suthar Michael Gale Edward A Clark |
| author_sort | Kelsey Roe |
| collection | DOAJ |
| description | Mitochondrial antiviral signaling protein (MAVS) is a critical innate immune signaling protein that directs the actions of the RIG-I-like receptor (RLR) signaling pathway of RNA virus recognition and initiation of anti-viral immunity against West Nile virus (WNV). In the absence of MAVS, mice die more rapidly after infection with the pathogenic WNV-Texas (TX) strain, but also produce elevated WNV-specific IgG concomitant with increased viral burden. Here we investigated whether there was a B cell intrinsic role for MAVS during the development of protective humoral immunity following WNV infection. MAVS-/- mice survived infection from the non-pathogenic WNV-Madagascar (MAD) strain, with limited signs of disease. Compared to wildtype (WT) controls, WNV-MAD-infected MAVS-/- mice had elevated serum neutralizing antibodies, splenic germinal center B cells, plasma cells and effector T cells. We found that when rechallenged with the normally lethal WNV-TX, MAVS-/- mice previously infected with WNV-MAD were protected from disease. Thus, protective humoral and cellular immune responses can be generated in absence of MAVS. Mice with a conditional deletion of MAVS only in CD11c+ dendritic cells phenocopied MAVS whole body knockout mice in their humoral responses to WNV-MAD, displaying elevated virus titers and neutralizing antibodies. Conversely, a B cell-specific deletion of MAVS had no effect on immune responses to WNV-MAD compared to WT controls. Thus, MAVS in dendritic cells is required to control WNV replication and thereby regulate downstream humoral immune responses. |
| first_indexed | 2024-12-16T10:03:16Z |
| format | Article |
| id | doaj.art-66befa0a707347bd8decaa0941664a8b |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-16T10:03:16Z |
| publishDate | 2019-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-66befa0a707347bd8decaa0941664a8b2022-12-21T22:35:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01146e021892810.1371/journal.pone.0218928Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses.Kelsey RoeDaniela GiordanoLucy B YoungKevin E DravesUrsula HolderMehul S SutharMichael GaleEdward A ClarkMitochondrial antiviral signaling protein (MAVS) is a critical innate immune signaling protein that directs the actions of the RIG-I-like receptor (RLR) signaling pathway of RNA virus recognition and initiation of anti-viral immunity against West Nile virus (WNV). In the absence of MAVS, mice die more rapidly after infection with the pathogenic WNV-Texas (TX) strain, but also produce elevated WNV-specific IgG concomitant with increased viral burden. Here we investigated whether there was a B cell intrinsic role for MAVS during the development of protective humoral immunity following WNV infection. MAVS-/- mice survived infection from the non-pathogenic WNV-Madagascar (MAD) strain, with limited signs of disease. Compared to wildtype (WT) controls, WNV-MAD-infected MAVS-/- mice had elevated serum neutralizing antibodies, splenic germinal center B cells, plasma cells and effector T cells. We found that when rechallenged with the normally lethal WNV-TX, MAVS-/- mice previously infected with WNV-MAD were protected from disease. Thus, protective humoral and cellular immune responses can be generated in absence of MAVS. Mice with a conditional deletion of MAVS only in CD11c+ dendritic cells phenocopied MAVS whole body knockout mice in their humoral responses to WNV-MAD, displaying elevated virus titers and neutralizing antibodies. Conversely, a B cell-specific deletion of MAVS had no effect on immune responses to WNV-MAD compared to WT controls. Thus, MAVS in dendritic cells is required to control WNV replication and thereby regulate downstream humoral immune responses.https://doi.org/10.1371/journal.pone.0218928 |
| spellingShingle | Kelsey Roe Daniela Giordano Lucy B Young Kevin E Draves Ursula Holder Mehul S Suthar Michael Gale Edward A Clark Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. PLoS ONE |
| title | Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. |
| title_full | Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. |
| title_fullStr | Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. |
| title_full_unstemmed | Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. |
| title_short | Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses. |
| title_sort | dendritic cell associated mavs is required to control west nile virus replication and ensuing humoral immune responses |
| url | https://doi.org/10.1371/journal.pone.0218928 |
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