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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2888-2897 |
| Number of pages | 10 |
| Journal | Journal of Clinical Investigation |
| Volume | 129 |
| Issue number | 7 |
| DOIs | |
| State | Published - Apr 30 2019 |
Bibliographical note
Funding Information:We are grateful to members of the Inflammation Program, Eric Elliott, Mary Wilson, Diogo Valadares, and Bruce Hostager (University of Iowa, Iowa City) for valuable discussions and technical assistance. We thank Beng San Yeoh and Matam Vijay-Kumar (University of Toledo) for providing Nlrc4-/- femurs. We thank members of the University of Iowa Flow Cytometry Facility, a Carver College of Medicine/Holden Comprehensive Cancer Center core research facility, for their expertise. NIH grants R01 AI118719 (to FSS), R01 AI104706 (to SLC), and T32 AI007485 (to EEH and AMM) and a grant from the Harry J. Lloyd Charitable Trust (to FSS) supported this work. This material is the result of work supported in part with resources and the use of facilities at the Iowa City Veterans Administration Medical Center. The contents of this report do not represent the views of the Veterans Administration or the United States Government.
Funding Information:
We are grateful to members of the Inflammation Program, Eric Elliott, Mary Wilson, Diogo Valadares, and Bruce Hostager (University of Iowa, Iowa City) for valuable discussions and technical assistance. We thank Beng San Yeoh and Matam Vijay-Kumar (University of Toledo) for providing Nlrc4–/– femurs. We thank members of the University of Iowa Flow Cytometry Facility, a Carver College of Medicine/Holden Comprehensive Cancer Center core research facility, for their expertise. NIH grants R01 AI118719 (to FSS), R01 AI104706 (to SLC), and T32 AI007485 (to EEH and AMM) and a grant from the Harry J. Lloyd Charitable Trust (to FSS) supported this work. This material is the result of work supported in part with resources and the use of facilities at the Iowa City Veterans Administration Medical Center. The contents of this report do not represent the views of the Veterans Administration or the United States Government.
Publisher Copyright:
© 2019, American Society for Clinical Investigation.