Journal article
Dendritic cell NLRC4 regulates influenza A virus–specific CD4+ T cell responses through FasL expression
The Journal of clinical investigation, Vol.129(7), pp.2888-2897
2019
DOI: 10.1172/JCI124937
PMCID: PMC6597209
PMID: 31038471
Abstract
Influenza A virus–specific (IAV-specific) T cell responses are important correlates of protection during primary and subsequent infections. The 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 the 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 with WT 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 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.
Details
- Title: Subtitle
- Dendritic cell NLRC4 regulates influenza A virus–specific CD4+ T cell responses through FasL expression
- Creators
- Emma E Hornick - University of IowaJargalsaikhan Dagvadorj - Cedars-Sinai Medical CenterZeb R Zacharias - University of IowaAnn M Miller - University of IowaRyan A Langlois - University of MinnesotaPeter Chen - Cedars-Sinai Medical CenterKevin L Legge - University of IowaGail A Bishop - University of IowaFayyaz S Sutterwala - University of IowaSuzanne L Cassel - University of Iowa
- Resource Type
- Journal article
- Publication Details
- The Journal of clinical investigation, Vol.129(7), pp.2888-2897
- Publisher
- American Society for Clinical Investigation
- DOI
- 10.1172/JCI124937
- PMID
- 31038471
- PMCID
- PMC6597209
- ISSN
- 0021-9738
- eISSN
- 1558-8238
- Grant note
- R01 AI104706 / ; T32 AI007485 / ; R01 AI118719 / ; no number / ;
- Language
- English
- Date published
- 2019
- Academic Unit
- Microbiology and Immunology; President; Pathology; Fraternal Order of Eagles Diabetes Research Center
- Record Identifier
- 9984186494102771
Metrics
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