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Vol. 16. Issue 1.
Pages 19-26 (January - February 2012)
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Vol. 16. Issue 1.
Pages 19-26 (January - February 2012)
Open Access
Effects of Epstein-Barr virus on the development of dendritic cells derived from cord blood monocytes: an essential role for apoptosis
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Juan-Juan Wanga,b, Yu-Feng Lib, Ying-Ying Jinb, Xi Wangb, Tong-Xin Chena,
Corresponding author
tongxinc@yahoo.com

Corresponding author at: Department of Clinical Immunology/Department of Nephrology and Rheumatology, Children's Hospital of Shanghai, Shanghai Jiao Tong University, 1400 Beijing Western Road, Shanghai 200040, China.
a Department of Clinical Immunology/Department of Nephrology and Rheumatology, Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai, China
b Department of Pediatrics, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Abstract
Objective

Epstein-Barr virus (EBV) is a ubiquitous human γ-herpes virus, which can adapt and evade host immune defense. Dendritic cells (DCs) play a pivotal role in the initiation and maintenance of immune responses. This study investigated the effects of EBV on cord blood monocytes derived DCs (CBDC).

Methods

Monocytes were isolated from cord blood and cultured in medium containing recombinant IL-4 and GM-CSF to induce DCs development. B95-8 supernatant was added in monocytes culture medium for EBV infection at day 0. Phenotypic characterization of DCs, apoptotic cells, and mitochondrial membrane potential (MMP) were detected by flow cytometry. The morphology was observed by Hoechst 33258 staining and TUNEL staining, the expression of X-linked inhibitor of apoptosis protein (XIAP) was detected by Western blotting assay and caspase 3, 8 and 9 activity was measured.

Results

Phenotypic characterization of DCs was changed in EBV-treated group. Chromatin condensation and DNA fragmentation were observed in EBV induced CBDC apoptosis. In addition, caspase 3, caspase 8, and caspase 9 activation were enhanced in the EBV-treated group. This was accompanied by the loss of MMP. Furthermore, XIAP expression was down-regulated in the EBV-treated group and compared to mock-infected group.

Conclusion

These results suggested that EBV could inhibit CBDC phenotypic differentiation, and induce CBDC apoptosis in caspase-dependent manner with involvement of the mitochondrial pathway. This might help EBV to evade host immune responses to establish persistent infection.

Keywords:
Dendritic cells
Apoptosis
Epstein-Barr virus infections
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References
[1.]
K. Kawa.
Epstein-Barr virus-associated diseases in humans.
Int J Hematol, 71 (2000), pp. 108-116
[2.]
R. Khanna, S.R. Burrows, D.J. Moss.
Immune regulation in Epstein-Barr virus-associated diseases.
Microbiol Rev, 59 (1995), pp. 387-395
[3.]
L. Li, D. Liu, L. Hutt-Fletcher, et al.
Epstein-Barr virus inhibits the development of dendritic cells by promoting apoptosis of their monocyte precursors in the presence of granulocyte macrophage-colony-stimulating factor and interleukin-4.
Blood, 99 (2002), pp. 3725-3734
[4.]
S. Salek-Ardakani, S.A. Lyons, J.R. Arrand.
Epstein-Barr virus promotes human monocyte survival and maturation through a paracrine induction of IFN-γ.
J Immunol, 173 (2004), pp. 321-331
[5.]
E. Liu, W. Tu, H.K. Law, et al.
Decreased yield, phenotypic expression and function of immature monocyte-derived dendritic cells in cord blood.
Br J Haematol, 113 (2001), pp. 240-246
[6.]
M.B. Lutz, G. Schuler.
Immature, semi-mature and fully mature dendritic cells: which signals induce tolerance or immunity?.
Trends Immunol, 23 (2002), pp. 445-449
[7.]
P. McGuirk, P.A. Johnson, E.J. Ryan, et al.
Filamentous hemagglutinin and pertussis toxin from Bordetella pertussis modulate immune responses to unrelated antigens.
J Infect Dis, 182 (2000), pp. 1286-1288
[8.]
D. Van der Kleij, E. Latz, J.F.H.M. Brouwers, et al.
A novel host-parasite lipid cross-talk, Schistosomal lyso-phosphatidylserine activates toll-like receptor 2 and affects immune polarization.
J Biol Chem, 277 (2002), pp. 48122-48129
[9.]
P. McGuirk, C. McCann, K.H. Mills.
Pathogen-specific T regulatory 1 cells induced in the respiratory tract by a bacterial molecule that stimulates interleukin 10 production by dendritic cells: a novel strategy for evasion of protective T helper type 1 responses by Bordetella pertussis.
J Exp Med, 195 (2002), pp. 221-231
[10.]
C. Servet-Delprat, P.-O. Vidalain, H. Bausinger, et al.
Measles virus induces abnormal differentiation of CD40 ligand-activated human dendritic cells.
J Immunol, 164 (2000), pp. 1753-1760
[11.]
J. Schnorr Jr., S. Xanthakos, P. Keikavoussi, et al.
Induction of maturation of human blood dendritic cell precursors by measles virus is associated with immunosuppression.
Proc Natl Acad Sci USA, 94 (1997), pp. 5326-5331
[12.]
J.C. Marie, J. Kehren, M.-C. Trescol-Biémont, et al.
Mechanism of measles virus-induced suppression of inflammatory immune responses.
Immunity, 14 (2001), pp. 69-79
[13.]
E. Kieff.
Epstein-Barr virus and its replication.
Fields Virology, 3rd ed., pp. 2343-2396
[14.]
C.D. Gregory, C. Dive, S. Henderson.
Activation of Epstein-Barr virus latent genes protects human B cells from death by apoptosis.
Nature, 349 (1991), pp. 612-614
[15.]
Y. Shi.
Mechanisms of caspase activation and inhibition during apoptosis.
Mol Cell, 9 (2002), pp. 459-470
[16.]
G.S. Salvesen, C.S. Duckett.
IAP proteins: blocking the road to death's door.
Nature Rev Mol Cell Biol, 3 (2002), pp. 401-410
[17.]
J.K. Maier, Z. Lahoua, N.H. Gendron, et al.
The neuronal apoptosis inhibitory protein is a direct inhibitor of caspases 3 and 7.
J Neurosci, 22 (2002), pp. 2035-2043
[18.]
M. Rescigno, M. Martino, C.L. Sutherland, et al.
Dendritic cell survival and maturation are regulated by different signaling pathways.
J Exp Med, 188 (1998), pp. 2175-2180
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