Journal article
Lymphopenia associated with highly virulent H5N1 virus infection due to plasmacytoid dendritic cell-mediated apoptosis of T cells
The Journal of immunology (1950), Vol.192(12), pp.5906-5912
06/15/2014
DOI: 10.4049/jimmunol.1302992
PMCID: PMC4083746
PMID: 24829418
Abstract
Although lymphopenia is a hallmark of severe infection with highly pathogenic H5N1 and the newly emerged H7N9 influenza viruses in humans, the mechanism(s) by which lethal H5N1 viruses cause lymphopenia in mammalian hosts remains poorly understood. Because influenza-specific T cell responses are initiated in the lung draining lymph nodes (LNs), and lymphocytes subsequently traffic to the lungs or peripheral circulation, we compared the immune responses in the lung draining LNs postinfection with a lethal A/HK/483/97 or nonlethal A/HK/486/97 (H5N1) virus in a mouse model. We found that lethal H5N1, but not nonlethal H5N1, virus infection in mice enhances Fas ligand (FasL) expression on plasmacytoid dendritic cells (pDCs), resulting in apoptosis of influenza-specific CD8(+) T cells via a Fas-FasL-mediated pathway. We also found that pDCs, but not other DC subsets, preferentially accumulate in the lung draining LNs of lethal H5N1 virus-infected mice, and that the induction of FasL expression on pDCs correlates with high levels of IL-12p40 monomer/homodimer in the lung draining LNs. Our data suggest that one of the mechanisms of lymphopenia associated with lethal H5N1 virus infection involves a deleterious role for pDCs.
Details
- Title: Subtitle
- Lymphopenia associated with highly virulent H5N1 virus infection due to plasmacytoid dendritic cell-mediated apoptosis of T cells
- Creators
- Kobporn Boonnak - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892Leatrice Vogel - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892Friederike Feldmann - Veterinary Branch, Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840Heinz Feldmann - Laboratory of Virology, Rocky Mountain Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT 59840; andKevin L Legge - Department of Pathology, University of Iowa, Iowa City, IA 52242 KSUBBARAO@niaid.nih.gov kevin-legge@uiowa.eduKanta Subbarao - Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892; KSUBBARAO@niaid.nih.gov kevin-legge@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.192(12), pp.5906-5912
- DOI
- 10.4049/jimmunol.1302992
- PMID
- 24829418
- PMCID
- PMC4083746
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- United States
- Grant note
- R01 AI071085 / NIAID NIH HHS AI071085 / NIAID NIH HHS Intramural NIH HHS R56 AI071085 / NIAID NIH HHS
- Language
- English
- Date published
- 06/15/2014
- Academic Unit
- Microbiology and Immunology; Pathology
- Record Identifier
- 9984046929802771
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