HHV-8 reduces dendritic cell migration through down-regulation of cell-surface CCR6 and CCR7 and cytoskeleton reorganization

Virology Journal

Alberto Faggioni¹  Luigi Frati¹  Roberta Santarelli¹  Marisa Granato¹  Pankaj Trivedi¹  Sandro Valia¹  Antonella Farina¹  Valeria Conte¹  Mara Cirone¹ 

[1] Istituto Pasteur-Fondazione Cenci Bolognetti, Department of Experimental Medicine, La Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy

关键词: Dendritic cells.;    HHV-8;    Chemokine receptors;    Chemokines;   

Others  :  1154672
DOI  :  10.1186/1743-422X-9-92

 received in 2012-01-10, accepted in 2012-05-14,  发布年份 2012

【 摘 要 】

Background

For an efficient immune response against viral infection, dendritic cells (DCs) must express a coordinate repertoire of receptors that allow their recruitment to the sites of inflammation and subsequently to the secondary lymphoid organs in response to chemokine gradients.

Several pathogens are able to subvert the chemokine receptor expression and alter the migration properties of DCs as strategy to escape from the immune control.

Findings

Here we report the inhibitory effect of Human Herpesvirus 8 (HHV-8) on the migratory behavior of immature and mature DCs. We found that the virus altered the DC chemokine receptor expression and chemokine induced migration. Moreover HHV-8 was also able to interfere with basal motility of DCs by inducing cytoskeleton modifications.

Conclusion

Based on our findings, we suggest that HHV-8 is able to subvert the DC migration capacity and this represents an additional mechanism which interferes with their immune-functions.

【 授权许可】

   
2012 Cirone et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

Figure 4.

【 参考文献 】

• [1]Banchereau J, Breire F, Caux C, Davoust J, Lebecque S, Liu YJ, Puledran B, Palucka K: Immunobiology of dendritic cells. Annu Rev Immunol 2000, 18:767-811.
• [2]Sozzani S, Allavena P, Vecchi A, Mantovani A: Chemokines and dendritic cell traffic. J Clin Immunol 2000, 20:151-160.
• [3]Sozzani S, Luini W, Borsatti A, Polentarutti N, Zhou D, Piemonti L, D'Amico G, Power CA, Wells TN, Gobbi M, Allavena P, Mantovani A: Receptor expression and responsiveness of human dendritic cells to a defined set of CC and CXC chemokines. J Immunol 1997, 159:1993-2000.
• [4]Caux C, Ait-Yahia S, Chemin K, de Bouteiller O, Dieu-Nosjean MC, Homey B, Massacrier C, Vanbervliet B, Zlotnik A, Vicari A: Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Semin Immunopathol 2000, 22:345-369.
• [5]Kallal LE, Schaller MA, Lindell DM, Lira SA, Lukacs NW: CCL20/CCR6 blockade enhances immunity to RSV by impairing recruitment of DC. Eur J Immunol. 2010, 40:1042-1052.
• [6]Förster R, Davalos-Misslitz AC, Rot A: CCR7 and its ligands: balancing immunity and tolerance. Nat Rev Immunol 2008, 8:362-371.
• [7]Humrich JY, Thumann P, Greiner S, Humrich JH, Averbeck M, Schwank C, Kämpgen E, Schuler G, Jenne L: Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells. Eur J Immunol 2007, 37:954-965.
• [8]Grayson MH, Ramos MS, Rohlfing MM, Kitchens R, Wang HD, Gould A, Agapov E, Holtzman MJ: Controls for lung dendritic cell maturation and migration during respiratory viral infection. J Immunol 2007, 179:1438-1348.
• [9]Prechtel AT, Turza NM, Kobelt DJ, Eisemann JI, Coffin RS, McGrath Y, Hacker C, Ju X, Zenke M, Steinkasserer A: Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration. J Gen Virol 2005, 86:1645-1657.
• [10]Varani S, Frascaroli G, Homman-Loudiyi M, Feld S, Landini MP, Söderberg-Nauclér C: Human cytomegalovirus inhibits the migration of immature dendritic cells by down-regulating cell-surface CCR1 and CCR5. J Leukoc Biol 2005, 77:219-228.
• [11]Moutaftsi M, Brennan P, Spector SA, Tabi Z: Impaired lymphoid chemokine-mediated migration due to a block on the chemokine receptor switch in human cytomegalovirus-infected dendritic cells. J Virol 2004, 78:3046-3054.
• [12]Boshoff C, Weiss R: AIDS-related malignancies. Nat Rev Cancer 2002, 2:373-382.
• [13]Rappocciolo G, Jenkins FJ, Hensler HR, Piazza P, Jais M, Borowski L, Watkins SC, Rinaldo CR: DC-SIGN is a receptor for human herpesvirus 8 on dendritic cells and macrophages. J Immunol 2006, 17:1741-1749.
• [14]Cirone M, Lucania G, Bergamo P, Trivedi P, Frati L, Faggioni A: Human herpesvirus 8 (HHV-8) inhibits monocyte differentiation into dendritic cells and impairs their immunostimulatory activity. Immunol Lett 2007, 113:40-46.
• [15]Lallemand F, Desire N, Rozenbaum W, Nicolas JC, Marechal V: Quantitative analysis of human herpesvirus 8 viral load using a real-time PCR assay. J Clin Microbiol 2000, 38:1404-1408.
• [16]Schutyser E, Struyf S, Van Damme J: The CC chemokine CCL20 and its receptor CCR6. Cytokine Growth Factor Rev 2003, 14:409-426.
• [17]Allavena P, Sica A, Vecchi A, Locati M, Sozzani S, Mantovani A: The chemokine receptor switch paradigm and dendritic cell migration: its significance in tumor tissues. Immunol Rev 2000, 177:141-149.
• [18]Cunningham AL, Donaghy H, Harman AN, Kim M, Turville SG: Manipulation of dendritic cell function by viruses. Curr Opin Microbiol 2010, 13:524-529.
• [19]Hensler HR, Rappocciolo G, Rinaldo CR, Jenkins FJ: Cytokine production by human herpesvirus 8-infected cells. J Gen Virol 2009, 90:79-83.
• [20]Theodoridis AA, Eich C, Figdor CG, Steinkasserer A: Infection of dendritic cells with herpes simplex type 1 induces rapid degradation of CYTIP, thereby modulating adhesion and migration. Blood 2011, 118:105-115.
• [21]Nefedova Y, Huang M, Kusmartsev S, Battacharya R, Cheng P, Salup R, Jove R, Gabrilovich D: Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer. J. Immunol. 2004, 172:464-474.