树突状细胞与丙型肝炎病毒感染研究
冯志华, 李军, 中国人民解放军第四军医大学唐都医院 陕西省西安市 710038
冯志华, 女,1964-11-08生,山西省忻州市人,汉族,第四军医大学博士,硕士生导师,副教授、副主任医师.主要从事丙型病毒性肝炎治疗性疫苗研究.主编及参编医学专著5部,获军队及省部级科技成果奖3项,负责及参与国家自然科学基金课题8项.
国家自然科学基金资助项目,No. 39800122, No. 30170822
项目负责人: 冯志华,710038, 陕西省西安市,中国人民解放军第四军医大学唐都医院. Fengzh@fmmu.edu.cn
电话:029-83377165 传真: 029-83377165
, 百拇医药
收稿日期:2005-01-06 接受日期: 2005-01-20
摘要
树突状细胞(DC)在捕获丙型肝炎病毒(HCV)并向靶器官传播的过程中扮演了重要的角色.本文就病毒感染前后DC的作用及功能变化，尤其是HCV感染过程中，DC可能通过其表面特异性C型凝集素-细胞间黏附分子3结合非整合素分子(DCspecific intercellular adhesion molecule 3-grabbing nonintegrin，DC-SIGN)保护病毒转运、促进病毒感染靶细胞的路径，DC-SIGN可能将HCV传递给肝细胞以及B或T淋巴细胞亚群等做一简要的综述.
关键词:树突状细胞;丙型肝炎病毒
冯志华,李军. 树突状细胞与丙型肝炎病毒感染研究.世界华人消化杂志 2005;13(5):588-5911 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245-252
, 百拇医药
2 Feng ZH, Wang QC, Nie QH, Jia ZS, Zhou YX. DC-SIGN:Binding receptor for HCV? World J Gastroenterol
2004;10:925-929
3 Cameron PU, Freudenthal PS, Barker JM, Gezelter S, Inaba K, Steinman RM. Dendritic cells exposed to human
immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 1992;257:383-387
4 Pope M, Betjes MG, Romani N, Hirmand H, Cameron PU, Hoffman L, Gezelter S, Schuler G, Steinman RM. Conjugates
, 百拇医药
of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994;78:389-398
5 Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS,KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that
enhances trans-infection of T cells. Cell 2000;100:587-597
, 百拇医药
6 Kudo S, Matsuno K, Ezaki T, Ogawa M. A novel migration pathway for rat dendritic cells from the blood:hepatic
sinusoids-lymph translocation. J Exp Med 1997;185:777-784
7 Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, Fieschi F, Arenzana-Seisdedos F, Moreau JF,Dechanet-Merville J. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell
, http://www.100md.com
trans-infection. Immunity 2002;17:653-664
8 Alvarez CP, Lasala F, Carrillo J, Muniz O, Corbi AL, Delgado R. C-type lectins DC-SIGN and L-SIGN mediate cellular entry
by Ebola virus in cis and in trans. J Virol 2002;76:6841-6844
9 Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, Subbarao K, Nabel GJ. pH-dependent entry of severe
acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer
, http://www.100md.com
through DC-SIGN. J Virol 2004;78:5642-5650
10 Appelmelk BJ, van Die I, van Vliet SJ, Vandenbroucke-Grauls CM, Geijtenbeek TB, van Kooyk Y. Cutting edge:
carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin
on dendritic cells. J Immunol 2003;170:1635-1639
11 Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B,Van Kooyk Y. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med 2003;197:717
, 百拇医药
12 Colmenares M, Puig-Kroger A, Pello OM, Corbi AL, Rivas L. Dendritic cell(DC)-specific intercellular adhesion
molecule 3(ICAM-3)-grabbing nonintegrin(DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor
for Leishmania amastigotes. J Biol Chem 2002;277:36766-36769
13 van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB, van Kooyk Y. The dendritic
, http://www.100md.com
cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan
antigen Lewis-x. Glycobiology 2003;13:471-478
14 Kanto T, Inoue M, Miyatake H, Sato A, Sakakibara M, Yakushijin T, Oki C, Itose I, Hiramatsu N, Takehara T,Kasahara A, Hayashi N. Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize
T helper cells in chronic hepatitis C virus infection. J Infect Dis 2004;190:1919-1926
, 百拇医药
15 Murakami H, Akbar SM, Matsui H, Horiike N, Onji M. Decreased interferon-alpha production and impaired T helper 1
polarization by dendritic cells from patients with chronic hepatitis C. Clin Exp Immunol 2004;137:559-565
16 冯志华, 王全楚, 周永兴, 郝春秋, 聂青和. HCV-Fc 融合基因疫苗真核表达载体的构建及表达.
世界华人消化杂志 2003;11:697-700
17 Wang QC, Feng ZH, Zhou YX, Nie QH. Induction of hepatitis Cvirus-specific cytotoxic T and B cell responses by
, http://www.100md.com
dendritic cells expressing a modified antigen targeting receptor. World J Gastroenterol 2005;11:557-560
18 Lozach PY, Amara A, Bartosch B, Virelizier JL, Arenzana-SeisdedosF, Cosset FL, Altmeyer R. C-type lectins L-SIGN
and DC-SIGN capture and transmit infectious hepatitis C viruspseudotype particles. J Biol Chem
2004;279:32035-32045
19 Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Krieger E, VriendG, Figdor CG, van Kooyk Y. Identification of
, http://www.100md.com
different binding sites in the dendritic cell-specific receptorDC-SIGN for intercellular adhesion molecule 3 and HIV-1.
J Biol Chem 2002;277:11314-11320
20 Pohlmann S, Soilleux EJ, Baribaud F, Leslie GJ, Morris LS,Trowsdale J, Lee B, Coleman N, Doms RW. DC-SIGNR,a DC-SIGN homologue expressed in endothelial cells, binds to humanand simian immunodeficiency viruses and
activates infection in trans. Proc Natl Acad Sci USA 2001;98:2670-2675
, 百拇医药
21 Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ,Eilering JB, Martin MP, Wu L, Martin TD, Viebig N,Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. A dendriticcell-specific intercellular adhesion molecule 3-
grabbing nonintegrin(DC-SIGN)-related protein is highly expressedon human liver sinusoidal endothelial cells and
promotes HIV-1 infection. J Exp Med 2001;193:671-678
, http://www.100md.com 22 Soilleux EJ, Morris LS, Lee B, Pohlmann S, Trowsdale J, Doms RW,Coleman N. Placental expression of DC-SIGN
may mediate intrauterine vertical transmission of HIV. J Pathol 2001;195:586-592
23 Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T,Olson WC. L-SIGN(CD 209L)is a liver-specific
capture receptor for hepatitis C virus. Proc Natl Acad Sci USA 2003;100:4498-4503
, 百拇医药
24 Feinberg H, Mitchell DA, Drickamer K, Weis WI. Structural basis forselective recognition of oligosaccharides by
DC-SIGN and DC-SIGNR. Science 2001;294:2163-2166
25 Mitchell DA, Fadden AJ, Drickamer K. A novel mechanism ofcarbohydrate recognition by the C-type lectins DC-SIGN
and DC-SIGNR. Subunit organization and binding to multivalentligands. J Biol Chem 2001;276:28939-28945
, 百拇医药
26 Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I,Foung S, Amara A, Houles C, Fieschi F,Schwartz O, Virelizier JL, Arenzana-Seisdedos F, Altmeyer R.DC-SIGN and L-SIGN are high affinity binding receptors
for hepatitis C virus glycoprotein E2. J Biol Chem 2003;278:20358-20366
27 Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie GJ, Lin G,Granelli-Piperno A, Doms RW, Rice CM, McKeating JA.
, 百拇医药
Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol 2003;77:4070-4080
28 Tassaneetrithep B, Burgess TH, Granelli-Piperno A, Trumpfheller C,Finke J, Sun W, Eller MA, Pattanapanyasat K,Sarasombath S, Birx DL, Steinman RM, Schlesinger S, Marovich MA.DC-SIGN(CD209)mediates dengue virus infection
of human dendritic cells. J Exp Med 2003;197:823-829
29 Cormier EG, Durso RJ, Tsamis F, Boussemart L, Manix C, Olson WC,Gardner JP, Dragic T. L-SIGN(CD209L)and
, http://www.100md.com
DC-SIGN(CD209)mediate transinfection of liver cells by hepatitis Cvirus. Proc Natl Acad Sci USA 2004;39:14067-14072
30 Wykes M, Pombo A, Jenkins C, MacPherson GG. Dendritic cellsinteract directly with naive B lymphocytes to transfer
antigen and initiate class switching in a primary T-dependentresponse. J Immunol 1998;161:1313-1319
31 Kushnir N, Liu L, MacPherson GG. Dendritic cells and resting Bcells form clusters in vitro and in vivo:T cell
, 百拇医药
independence, partial LFA-1 dependence, and regulation bycross-linking surface molecules. J Immunol
1998;160:1774-1781
32 Dubois B, Massacrier C, Caux C. Selective attraction of naive andmemory B cells by dendritic cells.
J Leukocyte Biol 2001;70:633-641
编辑 张海宁, 百拇医药( 冯志华, 李 军)
冯志华, 女,1964-11-08生,山西省忻州市人,汉族,第四军医大学博士,硕士生导师,副教授、副主任医师.主要从事丙型病毒性肝炎治疗性疫苗研究.主编及参编医学专著5部,获军队及省部级科技成果奖3项,负责及参与国家自然科学基金课题8项.
国家自然科学基金资助项目,No. 39800122, No. 30170822
项目负责人: 冯志华,710038, 陕西省西安市,中国人民解放军第四军医大学唐都医院. Fengzh@fmmu.edu.cn
电话:029-83377165 传真: 029-83377165
, 百拇医药
收稿日期:2005-01-06 接受日期: 2005-01-20
摘要
树突状细胞(DC)在捕获丙型肝炎病毒(HCV)并向靶器官传播的过程中扮演了重要的角色.本文就病毒感染前后DC的作用及功能变化，尤其是HCV感染过程中，DC可能通过其表面特异性C型凝集素-细胞间黏附分子3结合非整合素分子(DCspecific intercellular adhesion molecule 3-grabbing nonintegrin，DC-SIGN)保护病毒转运、促进病毒感染靶细胞的路径，DC-SIGN可能将HCV传递给肝细胞以及B或T淋巴细胞亚群等做一简要的综述.
关键词:树突状细胞;丙型肝炎病毒
冯志华,李军. 树突状细胞与丙型肝炎病毒感染研究.世界华人消化杂志 2005;13(5):588-5911 Banchereau J, Steinman RM. Dendritic cells and the control of immunity. Nature 1998;392:245-252
, 百拇医药
2 Feng ZH, Wang QC, Nie QH, Jia ZS, Zhou YX. DC-SIGN:Binding receptor for HCV? World J Gastroenterol
2004;10:925-929
3 Cameron PU, Freudenthal PS, Barker JM, Gezelter S, Inaba K, Steinman RM. Dendritic cells exposed to human
immunodeficiency virus type-1 transmit a vigorous cytopathic infection to CD4+ T cells. Science 1992;257:383-387
4 Pope M, Betjes MG, Romani N, Hirmand H, Cameron PU, Hoffman L, Gezelter S, Schuler G, Steinman RM. Conjugates
, 百拇医药
of dendritic cells and memory T lymphocytes from skin facilitate productive infection with HIV-1. Cell 1994;78:389-398
5 Geijtenbeek TB, Kwon DS, Torensma R, van Vliet SJ, van Duijnhoven GC, Middel J, Cornelissen IL, Nottet HS,KewalRamani VN, Littman DR, Figdor CG, van Kooyk Y. DC-SIGN, a dendritic cell-specific HIV-1-binding protein that
enhances trans-infection of T cells. Cell 2000;100:587-597
, 百拇医药
6 Kudo S, Matsuno K, Ezaki T, Ogawa M. A novel migration pathway for rat dendritic cells from the blood:hepatic
sinusoids-lymph translocation. J Exp Med 1997;185:777-784
7 Halary F, Amara A, Lortat-Jacob H, Messerle M, Delaunay T, Houles C, Fieschi F, Arenzana-Seisdedos F, Moreau JF,Dechanet-Merville J. Human cytomegalovirus binding to DC-SIGN is required for dendritic cell infection and target cell
, http://www.100md.com
trans-infection. Immunity 2002;17:653-664
8 Alvarez CP, Lasala F, Carrillo J, Muniz O, Corbi AL, Delgado R. C-type lectins DC-SIGN and L-SIGN mediate cellular entry
by Ebola virus in cis and in trans. J Virol 2002;76:6841-6844
9 Yang ZY, Huang Y, Ganesh L, Leung K, Kong WP, Schwartz O, Subbarao K, Nabel GJ. pH-dependent entry of severe
acute respiratory syndrome coronavirus is mediated by the spike glycoprotein and enhanced by dendritic cell transfer
, http://www.100md.com
through DC-SIGN. J Virol 2004;78:5642-5650
10 Appelmelk BJ, van Die I, van Vliet SJ, Vandenbroucke-Grauls CM, Geijtenbeek TB, van Kooyk Y. Cutting edge:
carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin
on dendritic cells. J Immunol 2003;170:1635-1639
11 Geijtenbeek TB, Van Vliet SJ, Koppel EA, Sanchez-Hernandez M, Vandenbroucke-Grauls CM, Appelmelk B,Van Kooyk Y. Mycobacteria target DC-SIGN to suppress dendritic cell function. J Exp Med 2003;197:717
, 百拇医药
12 Colmenares M, Puig-Kroger A, Pello OM, Corbi AL, Rivas L. Dendritic cell(DC)-specific intercellular adhesion
molecule 3(ICAM-3)-grabbing nonintegrin(DC-SIGN, CD209), a C-type surface lectin in human DCs, is a receptor
for Leishmania amastigotes. J Biol Chem 2002;277:36766-36769
13 van Die I, van Vliet SJ, Nyame AK, Cummings RD, Bank CM, Appelmelk B, Geijtenbeek TB, van Kooyk Y. The dendritic
, http://www.100md.com
cell-specific C-type lectin DC-SIGN is a receptor for Schistosoma mansoni egg antigens and recognizes the glycan
antigen Lewis-x. Glycobiology 2003;13:471-478
14 Kanto T, Inoue M, Miyatake H, Sato A, Sakakibara M, Yakushijin T, Oki C, Itose I, Hiramatsu N, Takehara T,Kasahara A, Hayashi N. Reduced numbers and impaired ability of myeloid and plasmacytoid dendritic cells to polarize
T helper cells in chronic hepatitis C virus infection. J Infect Dis 2004;190:1919-1926
, 百拇医药
15 Murakami H, Akbar SM, Matsui H, Horiike N, Onji M. Decreased interferon-alpha production and impaired T helper 1
polarization by dendritic cells from patients with chronic hepatitis C. Clin Exp Immunol 2004;137:559-565
16 冯志华, 王全楚, 周永兴, 郝春秋, 聂青和. HCV-Fc 融合基因疫苗真核表达载体的构建及表达.
世界华人消化杂志 2003;11:697-700
17 Wang QC, Feng ZH, Zhou YX, Nie QH. Induction of hepatitis Cvirus-specific cytotoxic T and B cell responses by
, http://www.100md.com
dendritic cells expressing a modified antigen targeting receptor. World J Gastroenterol 2005;11:557-560
18 Lozach PY, Amara A, Bartosch B, Virelizier JL, Arenzana-SeisdedosF, Cosset FL, Altmeyer R. C-type lectins L-SIGN
and DC-SIGN capture and transmit infectious hepatitis C viruspseudotype particles. J Biol Chem
2004;279:32035-32045
19 Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ, Krieger E, VriendG, Figdor CG, van Kooyk Y. Identification of
, http://www.100md.com
different binding sites in the dendritic cell-specific receptorDC-SIGN for intercellular adhesion molecule 3 and HIV-1.
J Biol Chem 2002;277:11314-11320
20 Pohlmann S, Soilleux EJ, Baribaud F, Leslie GJ, Morris LS,Trowsdale J, Lee B, Coleman N, Doms RW. DC-SIGNR,a DC-SIGN homologue expressed in endothelial cells, binds to humanand simian immunodeficiency viruses and
activates infection in trans. Proc Natl Acad Sci USA 2001;98:2670-2675
, 百拇医药
21 Bashirova AA, Geijtenbeek TB, van Duijnhoven GC, van Vliet SJ,Eilering JB, Martin MP, Wu L, Martin TD, Viebig N,Knolle PA, KewalRamani VN, van Kooyk Y, Carrington M. A dendriticcell-specific intercellular adhesion molecule 3-
grabbing nonintegrin(DC-SIGN)-related protein is highly expressedon human liver sinusoidal endothelial cells and
promotes HIV-1 infection. J Exp Med 2001;193:671-678
, http://www.100md.com 22 Soilleux EJ, Morris LS, Lee B, Pohlmann S, Trowsdale J, Doms RW,Coleman N. Placental expression of DC-SIGN
may mediate intrauterine vertical transmission of HIV. J Pathol 2001;195:586-592
23 Gardner JP, Durso RJ, Arrigale RR, Donovan GP, Maddon PJ, Dragic T,Olson WC. L-SIGN(CD 209L)is a liver-specific
capture receptor for hepatitis C virus. Proc Natl Acad Sci USA 2003;100:4498-4503
, 百拇医药
24 Feinberg H, Mitchell DA, Drickamer K, Weis WI. Structural basis forselective recognition of oligosaccharides by
DC-SIGN and DC-SIGNR. Science 2001;294:2163-2166
25 Mitchell DA, Fadden AJ, Drickamer K. A novel mechanism ofcarbohydrate recognition by the C-type lectins DC-SIGN
and DC-SIGNR. Subunit organization and binding to multivalentligands. J Biol Chem 2001;276:28939-28945
, 百拇医药
26 Lozach PY, Lortat-Jacob H, de Lacroix de Lavalette A, Staropoli I,Foung S, Amara A, Houles C, Fieschi F,Schwartz O, Virelizier JL, Arenzana-Seisdedos F, Altmeyer R.DC-SIGN and L-SIGN are high affinity binding receptors
for hepatitis C virus glycoprotein E2. J Biol Chem 2003;278:20358-20366
27 Pohlmann S, Zhang J, Baribaud F, Chen Z, Leslie GJ, Lin G,Granelli-Piperno A, Doms RW, Rice CM, McKeating JA.
, 百拇医药
Hepatitis C virus glycoproteins interact with DC-SIGN and DC-SIGNR. J Virol 2003;77:4070-4080
28 Tassaneetrithep B, Burgess TH, Granelli-Piperno A, Trumpfheller C,Finke J, Sun W, Eller MA, Pattanapanyasat K,Sarasombath S, Birx DL, Steinman RM, Schlesinger S, Marovich MA.DC-SIGN(CD209)mediates dengue virus infection
of human dendritic cells. J Exp Med 2003;197:823-829
29 Cormier EG, Durso RJ, Tsamis F, Boussemart L, Manix C, Olson WC,Gardner JP, Dragic T. L-SIGN(CD209L)and
, http://www.100md.com
DC-SIGN(CD209)mediate transinfection of liver cells by hepatitis Cvirus. Proc Natl Acad Sci USA 2004;39:14067-14072
30 Wykes M, Pombo A, Jenkins C, MacPherson GG. Dendritic cellsinteract directly with naive B lymphocytes to transfer
antigen and initiate class switching in a primary T-dependentresponse. J Immunol 1998;161:1313-1319
31 Kushnir N, Liu L, MacPherson GG. Dendritic cells and resting Bcells form clusters in vitro and in vivo:T cell
, 百拇医药
independence, partial LFA-1 dependence, and regulation bycross-linking surface molecules. J Immunol
1998;160:1774-1781
32 Dubois B, Massacrier C, Caux C. Selective attraction of naive andmemory B cells by dendritic cells.
J Leukocyte Biol 2001;70:633-641
编辑 张海宁, 百拇医药( 冯志华, 李 军)
