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J Clin Invest. 2019 Apr 30;130. pii: 124937. doi: 10.1172/JCI124937.
Dendritic cell NLRC4 regulates influenza A virus-specific CD4 T cell responses through FasL expression.
Hornick EE, Dagvadorj J, Zacharias ZR, Miller AM, Langlois RA, Chen P, Legge KL, Bishop GA, Sutterwala FS, Cassel SL.
Abstract
Influenza A virus (IAV)-specific T cell responses are important correlates of protection during primary and subsequent infections. Generation and maintenance of robust IAV-specific T cell responses relies on T cell interactions with dendritic cells (DCs). In this study, we explore the role of nucleotide-binding domain leucine-rich repeat containing receptor family member NLRC4 in modulating the DC phenotype during IAV infection. Nlrc4-/- mice had worsened survival and increased viral titers during infection, normal innate immune cell recruitment and IAV-specific CD8 T cell responses, but severely blunted IAV-specific CD4 T cell responses compared to wild-type mice. The defect in the pulmonary IAV-specific CD4 T cell response was not a result of defective priming or migration of these cells in Nlrc4-/- mice but was instead due to an increase in FasL+ DCs, resulting in IAV-specific CD4 T cell death. Together, our data support a novel role for NLRC4 in regulating the phenotype of lung DCs during a respiratory viral infection, and thereby influencing the magnitude of protective T cell responses.
KEYWORDS:
Adaptive immunity; Dendritic cells; Immunology; Influenza; Virology
PMID: 31038471 DOI: 10.1172/JCI124937
Free full text
Dendritic cell NLRC4 regulates influenza A virus-specific CD4 T cell responses through FasL expression.
Hornick EE, Dagvadorj J, Zacharias ZR, Miller AM, Langlois RA, Chen P, Legge KL, Bishop GA, Sutterwala FS, Cassel SL.
Abstract
Influenza A virus (IAV)-specific T cell responses are important correlates of protection during primary and subsequent infections. Generation and maintenance of robust IAV-specific T cell responses relies on T cell interactions with dendritic cells (DCs). In this study, we explore the role of nucleotide-binding domain leucine-rich repeat containing receptor family member NLRC4 in modulating the DC phenotype during IAV infection. Nlrc4-/- mice had worsened survival and increased viral titers during infection, normal innate immune cell recruitment and IAV-specific CD8 T cell responses, but severely blunted IAV-specific CD4 T cell responses compared to wild-type mice. The defect in the pulmonary IAV-specific CD4 T cell response was not a result of defective priming or migration of these cells in Nlrc4-/- mice but was instead due to an increase in FasL+ DCs, resulting in IAV-specific CD4 T cell death. Together, our data support a novel role for NLRC4 in regulating the phenotype of lung DCs during a respiratory viral infection, and thereby influencing the magnitude of protective T cell responses.
KEYWORDS:
Adaptive immunity; Dendritic cells; Immunology; Influenza; Virology
PMID: 31038471 DOI: 10.1172/JCI124937
Free full text