MicroRNA-155 Modulates the Pathogen Binding Ability of Dendritic Cells (DCs) by Down-regulation of DC-specific Intercellular Adhesion Molecule-3 Grabbing Non-integrin (DC-SIGN)

被引:187
作者
Martinez-Nunez, Rocio T. [1 ]
Louafi, Fethi [1 ]
Friedmann, Peter S. [1 ]
Sanchez-Elsner, Tilman [1 ]
机构
[1] Univ Southampton, Sch Med, Div Infect Inflammat & Repair, Southampton SO16 6YD, Hants, England
关键词
COLONY-STIMULATING FACTOR; T-CELLS; (ICAM-3)-GRABBING NONINTEGRIN; TRANS-INFECTION; RECEPTOR; PU.1; TRANSCRIPTION; MACROPHAGE; EXPRESSION; ANTIGEN;
D O I
10.1074/jbc.M109.011601
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
MicroRNA-155 (miR-155) has been involved in the response to inflammation in macrophages and lymphocytes. Here we show how miR-155 participates in the maturation of human dendritic cells (DC) and modulates pathogen binding by down-regulating DC-specific intercellular adhesion molecule-3 grabbing non-integrin (DC-SIGN), after directly targeting the transcription factor PU.1. During the maturation of DCs, miR-155 increases up to 130-fold, whereas PU.1 protein levels decrease accordingly. We establish that human PU.1 is a direct target for miR-155 and localize the target sequence for miR-155 in the 3'-untranslated region of PU.1. Also, overexpression of miR-155 in the THP1 monocytic cell line decreases PU.1 protein levels and DC-SIGN at both the mRNA and protein levels. We prove a link between the down-regulation of PU.1 and reduced transcriptional activity of the DC-SIGN promoter, which is likely to be the basis for its reduced mRNA expression, after miR-155 overexpression. Finally, we show that, by reducing DC-SIGN in the cellular membrane, miR-155 is involved in regulating pathogen binding as dendritic cells exhibited the lower binding capacity for fungi and HIV protein gp-120 when the levels of miR-155 were higher. Thus, our results suggest a mechanism by which miR-155 regulates proteins involved in the cellular immune response against pathogens that could have clinical implications in the way pathogens enter the human organism.
引用
收藏
页码:16334 / 16342
页数:9
相关论文
共 45 条
[1]   C-type lectins DC-SIGN and L-SIGN mediate cellular entry by Ebola virus in cis and in trans [J].
Alvarez, CP ;
Lasala, F ;
Carrillo, J ;
Muñiz, O ;
Corbí, AL ;
Delgado, R .
JOURNAL OF VIROLOGY, 2002, 76 (13) :6841-6844
[2]   Myeloid development is selectively disrupted in PU.1 null mice [J].
Anderson, KL ;
Smith, KA ;
Conners, K ;
McKercher, SR ;
Maki, RA ;
Torbett, BE .
BLOOD, 1998, 91 (10) :3702-3710
[3]   DC-SIGN-mediated infectious synapse formation enhances X4 HIV-1 transmission from dendritic cells to T cells [J].
Arrighi, JF ;
Pion, M ;
Garcia, E ;
Escola, JM ;
van Kooyk, Y ;
Geijtenbeek, TB ;
Piguet, V .
JOURNAL OF EXPERIMENTAL MEDICINE, 2004, 200 (10) :1279-1288
[4]   Balance of MafB and PU.1 specifies alternative macrophage or dendritic cell fate [J].
Bakri, Y ;
Sarrazin, S ;
Mayer, UP ;
Tillmanns, S ;
Nerlov, C ;
Boned, A ;
Sieweke, MH .
BLOOD, 2005, 105 (07) :2707-2716
[5]   Dendritic cells and the control of immunity [J].
Banchereau, J ;
Steinman, RM .
NATURE, 1998, 392 (6673) :245-252
[6]   MicroRNAs: Genomics, biogenesis, mechanism, and function (Reprinted from Cell, vol 116, pg 281-297, 2004) [J].
Bartel, David P. .
CELL, 2007, 131 (04) :11-29
[7]   KRAB can repress lentivirus proviral transcription independently of integration site [J].
Bulliard, Yannick ;
Wiznerowicz, Maciej ;
Barde, Isabelle ;
Trono, Didier .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2006, 281 (47) :35742-35746
[8]   The C-type lectin DC-SIGN (CD209) is an antigen-uptake receptor for Candida albicans on dendritic cells [J].
Cambi, A ;
Gijzen, K ;
de Vries, JM ;
Torensma, R ;
Joosten, B ;
Adema, GJ ;
Netea, MG ;
Kullberg, BJ ;
Romani, L ;
Figdor, CG .
EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (02) :532-538
[9]   DC-SIGN ligation on dendritic cells results in ERK and PI3K activation and modulates cytokine production [J].
Caparros, Esther ;
Munoz, Pilar ;
Sierra-Filardi, Elena ;
Serrano-Gomez, Diego ;
Puig-Kroeger, Amaya ;
Rodriguez-Fernandez, Jose L. ;
Mellado, Mario ;
Sancho, Jaime ;
Zubiaur, Mercedes ;
Corbi, Angel L. .
BLOOD, 2006, 107 (10) :3950-3958
[10]   Origin, maturation and antigen presenting function of dendritic cells [J].
Cella, M ;
Sallusto, F ;
Lanzavecchia, A .
CURRENT OPINION IN IMMUNOLOGY, 1997, 9 (01) :10-16