Journal article
Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response
Journal of virology, Vol.90(6), pp.2830-2837
12/30/2015
DOI: 10.1128/JVI.02546-15
PMCID: PMC4810669
PMID: 26719269
Abstract
Following influenza A virus (IAV) infection, development of a robust IAV-specific CD8 T cell response is required for clearance of primary infection and enhances memory protection. Following IAV infection, plasmacytoid dendritic cells (pDC) or CD8α(+) DC regulate pulmonary effector CD8 T cell responses within the lung. Without this DC-T cell interaction, insufficient effector CD8 T cells are maintained in the lungs, leading to enhanced morbidity and mortality. Previous studies have demonstrated that pDC are capable of classical presentation or cross-presentation of IAV antigens and could potentially regulate IAV-specific CD8 T cell responses through either mechanism. Our results demonstrate that pDC from the lungs of donor mice infected with an IAV that is not able to replicate in hematopoietic cells (142t-IAV), unlike donor pDC isolated from the lungs of control infected mice, are not able to rescue the host IAV-specific CD8 T cell response from apoptosis. This indicates that pDC must utilize the direct presentation pathway for this rescue. This inability of pDC from 142t-IAV donors to rescue the IAV-specific CD8 T cell response is not due to differences in the overall ability of 142t-IAV to replicate within the lungs or generate defective viral genomes or to differences in levels of costimulatory molecules required for this interaction. We further demonstrate that bypassing the antigen presentation pathway by coating the 142t-IAV pDC with IAV peptide epitopes restores their ability to rescue the IAV-specific CD8 T cell response.
IAV continues to be a global health burden, infecting 5 to 20% of the global population annually. Continued investigation into the mechanisms that mediate protective immune responses against IAV is important to improving current vaccination and antiviral strategies antagonistic toward IAV. Our findings presented herein demonstrate a key requirement for pDC promotion of effector CD8 T cell survival: that rather than utilizing cross-presentation, pDC must be infected and utilize the endogenous pathway for presentation of antigens to CD8 T cells during in vivo IAV infections. This suggests that targeting presentation via the endogenous pathway in pDC could be important for the development of unique antiviral cellular therapies.
Details
- Title: Subtitle
- Plasmacytoid Dendritic Cells Require Direct Infection To Sustain the Pulmonary Influenza A Virus-Specific CD8 T Cell Response
- Creators
- Emily A Hemann - Immunology Graduate Program and Department of Pathology, University of Iowa, Iowa City, Iowa, USALouisa E Sjaastad - Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USARyan A Langlois - Department of Microbiology and Immunology, University of Minnesota, Minneapolis, Minnesota, USA Center for Immunology, University of Minnesota, Minneapolis, Minnesota, USAKevin L Legge - Immunology Graduate Program and Department of Pathology, University of Iowa, Iowa City, Iowa, USA Department of Microbiology, University of Iowa, Iowa City, Iowa, USA kevin-legge@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of virology, Vol.90(6), pp.2830-2837
- Publisher
- United States
- DOI
- 10.1128/JVI.02546-15
- PMID
- 26719269
- PMCID
- PMC4810669
- ISSN
- 0022-538X
- eISSN
- 1098-5514
- Grant note
- R01 AI071085 / NIAID NIH HHS AI071085 / NIAID NIH HHS R56 AI071085 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS T32 AI007533 / NIAID NIH HHS
- Language
- English
- Date published
- 12/30/2015
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984046906102771
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