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PLoS One. 2019 Jun 26;14(6):e0218928. doi: 10.1371/journal.pone.0218928. eCollection 2019.

Dendritic cell-associated MAVS is required to control West Nile virus replication and ensuing humoral immune responses.

Author information

1
Department of Immunology, University of Washington, Seattle, Washington, United States of America.
2
Emory Vaccine Center, Yerkes National Primate Research Center, Atlanta, Georgia, United States of America.
3
Department of Pediatrics, Division of Infectious Disease, Emory University School of Medicine, Atlanta, Georgia, United States of America.
4
Center for Innate Immunity and Immune Disease, University of Washington, Seattle, Washington, United States of America.

Abstract

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.

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