Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0020189
Title: Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by polyic in vivo
Authors: Fuertes Marraco S.A.
Scott C.L.
Bouillet P.
Ives A.
Masina S.
Vremec D.
Jansen E.S.
O'Reilly L.A.
Schneider P.
Fasel N.
Shortman K. 
Strasser A.
Acha-Orbea H.
Keywords: beta interferon
BH3 protein
BIM protein
CD11b antigen
interferon
polyinosinic polycytidylic acid
protein bcl 2
protein Bid
protein MAVS
protein Noxa
PUMA protein
signal peptide
toll like receptor 3
unclassified drug
animal cell
animal experiment
animal model
animal tissue
apoptosis
article
CD8+ T lymphocyte
cell death
cell survival
controlled study
cross presentation
cytotoxic lymphocyte
dendritic cell
drug effect
drug mechanism
female
flow cytometry
gene expression regulation
immune deficiency
immunomodulation
in vitro study
in vivo study
interferon induction
interferon production
leishmaniasis
lymphocyte count
male
mouse
nonhuman
protein function
spleen cell
T lymphocyte activation
T lymphocyte subpopulation
Mus
Issue Date: 2011
Citation: Fuertes Marraco S.A., Scott C.L., Bouillet P., Ives A., Masina S., Vremec D., Jansen E.S., O'Reilly L.A., Schneider P., Fasel N., Shortman K., Strasser A., Acha-Orbea H. (2011). Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by polyic in vivo. PLoS ONE 6 (6) : e20189. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0020189
Rights: Attribution 4.0 International
Abstract: Background: DC are activated by pathogen-associated molecular patterns (PAMPs), and this is pivotal for the induction of adaptive immune responses. Thereafter, the clearance of activated DC is crucial to prevent immune pathology. While PAMPs are of major interest for vaccine science due to their adjuvant potential, it is unclear whether and how PAMPs may affect DC viability. We aimed to elucidate the possible apoptotic mechanisms that control activated DC lifespan in response to PAMPs, particularly in vivo. Methodology/Principal Findings: We report that polyinosinic:polycytidylic acid (PolyIC, synthetic analogue of dsRNA) induces dramatic apoptosis of mouse splenic conventional DC (cDC) in vivo, predominantly affecting the CD8? subset, as shown by flow cytometry-based analysis of splenic DC subsets. Importantly, while Bim deficiency conferred only minor protection, cDC depletion was prevented in mice lacking Bim plus one of three other BH3-only proteins, either Puma, Noxa or Bid. Furthermore, we show that Type I Interferon (IFN) is necessary and sufficient for DC death both in vitro and in vivo, and that TLR3 and MAVS co-operate in IFNß production in vivo to induce DC death in response to PolyIC. Conclusions/Significance: These results demonstrate for the first time in vivo that apoptosis restricts DC lifespan following activation by PolyIC, particularly affecting the CD8? cDC subset. Such DC apoptosis is mediated by the overlapping action of pro-apoptotic BH3-only proteins, including but not solely involving Bim, and is driven by Type I IFN. While Type I IFNs are important anti-viral factors, CD8? cDC are major cross-presenting cells and critical inducers of CTL. We discuss such paradoxical finding on DC death with PolyIC/Type I IFN. These results could contribute to understand immunosuppression associated with chronic infection, and to the optimization of DC-based therapies and the clinical use of PAMPs and Type I IFNs. © 2011 Fuertes Marraco et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162047
ISSN: 19326203
DOI: 10.1371/journal.pone.0020189
Rights: Attribution 4.0 International
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