PMID- 18089731
OWN - NLM
STAT- MEDLINE
DCOM- 20080227
LR  - 20200228
IS  - 0022-1317 (Print)
IS  - 0022-1317 (Linking)
VI  - 89
IP  - Pt 1
DP  - 2008 Jan
TI  - Dendritic cell-induced apoptosis of human cytomegalovirus-infected fibroblasts 
      promotes cross-presentation of pp65 to CD8+ T cells.
PG  - 78-86
LID - 10.1099/vir.0.83278-0 [doi]
AB  - An efficient host response to human cytomegalovirus (HCMV) infection may depend 
      on rapid sensing of the infection by the innate immune response prior to 
      deployment of viral immunosubversive functions. Control of HCMV dissemination 
      could be ensured by apoptosis of cells immediately following infection. In the 
      present report, it is demonstrated that changes in the ratio of c-FLIP to FLICE 
      contributed to early sensitivity of HCMV-infected MRC5 fibroblasts to tumour 
      necrosis factor alpha (TNF-alpha), providing an innate response to infection. 
      Dendritic cells (DCs) co-cultured with HCMV-infected MRC5 cells acquired the 
      ability to secrete TNF-alpha in an amount sufficient to kill infected 
      fibroblasts. Blockage of TNF-alpha binding to its receptor on MRC5 cells with 
      soluble TNF-R reduced the number of dead, HCMV-infected fibroblasts ingested by 
      DCs, thus highlighting the impact of the apoptotic state of infected cells for 
      efficient loading of DCs. Those DCs loaded with antigens available early in 
      infection, such as input virion-associated pp65, could then engage antigen 
      processing for cross-presentation to specific CD8(+) T cells. Cross-presentation 
      was impaired when MRC5 cells were treated with the pan-caspase inhibitor ZVAD 
      before co-culture with DCs. Altogether, our data suggest that the innate killing 
      capacity of DCs at the early stage of infection plays a role in the activation of 
      anti-HCMV CD8(+) T cells.
FAU - Mandron, Marie
AU  - Mandron M
AD  - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, 
      France.
FAU - Martin, Helene
AU  - Martin H
AD  - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, 
      France.
FAU - Bonjean, Beatrice
AU  - Bonjean B
AD  - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, 
      France.
FAU - Lule, Jacqueline
AU  - Lule J
AD  - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, 
      France.
FAU - Tartour, Eric
AU  - Tartour E
AD  - EA4054, Universite Rene Descartes-Paris 5, Paris, France.
AD  - Laboratoire d'Immunologie, Hopital Europeen Georges Pompidou, Paris, France.
FAU - Davrinche, Christian
AU  - Davrinche C
AD  - INSERM, U563, Centre de Physiopathologie de Toulouse Purpan, F-31300 Toulouse, 
      France.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (Phosphoproteins)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Matrix Proteins)
RN  - 0 (cytomegalovirus matrix protein 65kDa)
SB  - IM
MH  - Apoptosis/*immunology
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Cell Line
MH  - Coculture Techniques
MH  - Cytomegalovirus/genetics/*immunology
MH  - Dendritic Cells/cytology/*immunology/physiology
MH  - Fibroblasts/cytology/physiology
MH  - Humans
MH  - Phosphoproteins/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Necrosis Factor-alpha/*biosynthesis/metabolism
MH  - Viral Matrix Proteins/*genetics
EDAT- 2007/12/20 09:00
MHDA- 2008/02/28 09:00
CRDT- 2007/12/20 09:00
PHST- 2007/12/20 09:00 [pubmed]
PHST- 2008/02/28 09:00 [medline]
PHST- 2007/12/20 09:00 [entrez]
AID - 10.1099/vir.0.83278-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2008 Jan;89(Pt 1):78-86. doi: 10.1099/vir.0.83278-0.