Toll-like receptor 2 suppresses immunity against Candida albicans through induction of IL-10 and regulatory T cells

被引:472
作者
Netea, MG
Sutmuller, R
Hermann, C
Van der Graaf, CAA
Van der Meer, JWM
van Krieken, JH
Hartung, T
Adema, G
Kullberg, BJ
机构
[1] Univ Nijmegen, Med Ctr St Radboud, Dept Med, NL-6500 HB Nijmegen, Netherlands
[2] Univ Nijmegen, Med Ctr St Radboud, Dept Tumor Immunol, NL-6500 HB Nijmegen, Netherlands
[3] Univ Nijmegen, Med Ctr St Radboud, Dept Pathol, NL-6500 HB Nijmegen, Netherlands
[4] Univ Nijmegen, Ctr Infect Dis, NL-6500 HB Nijmegen, Netherlands
[5] Univ Konstanz, Dept Biochem Pharmacol, D-7750 Constance, Germany
关键词
D O I
10.4049/jimmunol.172.6.3712
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Toll-like receptor (TLR) 2 and TLR4 play a pivotal role in recognition of Candida albicans. We demonstrate that TLR2(-/-) mice are more resistant to disseminated Candida infection, and this is associated with increased chemotaxis and enhanced candidacidal capacity of TLR2(-/-) macrophages. Although production of the proinflammatory cytokines TNF, IL-1alpha, and IL-1beta is normal, IL-10 release is severely impaired in the TLR2(-/-) mice. This is accompanied by a 50% decrease in the CD4(+)CD25(+) regulatory T (Treg) cell population in TLR2(-/-) mice. In vitro studies confirmed that enhanced survival of Treg cells was induced by TLR2 agonists. The deleterious role of Treg cells on the innate immune response during disseminated candidiasis was underscored by the improved resistance to this infection after depletion of Treg cells. In conclusion, C. albicans induces immunosuppression through TLR2-derived signals that mediate increased IL-10 production and survival of Treg cells. This represents a novel mechanism in the pathogenesis of fungal infections.
引用
收藏
页码:3712 / 3718
页数:7
相关论文
共 34 条
[1]   CD4+CD25+ regulatory T cells control Leishmania major persistence and immunity [J].
Belkaid, Y ;
Piccirillo, CA ;
Mendez, S ;
Shevach, EM ;
Sacks, DL .
NATURE, 2002, 420 (6915) :502-507
[2]   Dectin-1 is a major β-glucan receptor on macrophages [J].
Brown, GD ;
Taylor, PR ;
Reid, DM ;
Willment, JA ;
Williams, DL ;
Martinez-Pomares, L ;
Wong, SYC ;
Gordon, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2002, 196 (03) :407-412
[3]   Dectin-1 mediates the biological effects of β-glucans [J].
Brown, GD ;
Herre, J ;
Williams, DL ;
Willment, JA ;
Marshall, ASJ ;
Gordon, S .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (09) :1119-1124
[4]   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
[5]   DIFFERENTIAL-EFFECTS OF CD4+ AND CD8+ CELLS IN ACUTE, SYSTEMIC MURINE CANDIDOSIS [J].
COKER, LA ;
MERCADAL, CM ;
ROUSE, BT ;
MOORE, RN .
JOURNAL OF LEUKOCYTE BIOLOGY, 1992, 51 (03) :305-306
[6]   Toll-like receptor 2-deficient mice are highly susceptible to Streptococcus pneumoniae meningitis because of reduced bacterial clearing and enhanced inflammation [J].
Echchannaoui, H ;
Frei, K ;
Schnell, C ;
Leib, SL ;
Zimmerli, W ;
Landmann, R .
JOURNAL OF INFECTIOUS DISEASES, 2002, 186 (06) :798-806
[7]   Nosocomial bloodstream infections in United States hospitals: A three-year analysis [J].
Edmond, MB ;
Wallace, SE ;
McClish, DK ;
Pfaller, MA ;
Jones, RN ;
Wenzel, RP .
CLINICAL INFECTIOUS DISEASES, 1999, 29 (02) :239-244
[8]   Lymphocytes utilize CD11b/CD18 for adhesion to Candida albicans [J].
Forsyth, CB ;
Mathews, HL .
CELLULAR IMMUNOLOGY, 1996, 170 (01) :91-100
[9]  
Fulurija A, 1997, J MED VET MYCOL, V35, P197
[10]   Collaborative induction of inflammatory responses by dectin-1 and toll-like receptor 2 [J].
Gantner, BN ;
Simmons, RM ;
Canavera, SJ ;
Akira, S ;
Underhill, DM .
JOURNAL OF EXPERIMENTAL MEDICINE, 2003, 197 (09) :1107-1117