Inhibition of monocytic interleukin-12 production by Candida albicans via selective activation of ERK mitogen-activated protein kinase

被引:30
作者
Tang, NF
Liu, LM
Kang, KF
Mukherjee, PK
Takahara, M
Chen, GF
McCormick, TS
Cooper, KD
Ghannoum, M
机构
[1] Case Western Reserve Univ, Univ Hosp Cleveland, Dept Dermatol, Cleveland, OH 44106 USA
[2] Case Western Reserve Univ, Univ Hosp Cleveland, Ctr Med Mycol, Cleveland, OH 44106 USA
[3] Vet Affairs Med Ctr, Cleveland, OH USA
[4] Kyushu Univ, Dept Dermatol, Fukuoka 812, Japan
关键词
D O I
10.1128/IAI.72.5.2513-2520.2004
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Our previous data demonstrated that live Candida albicans inhibits interleukin-12 (IL-12) production by human monocytes. Here we explored whether C albicans inhibits IL-12 via a released factor and whether the inhibition is mediated via mitogen-activated protein kinase (MAPK) regulation. Supernatant fluids were obtained from cultured C albicans (SC5314) as well as cultured Saccharomyces cerevisiae after 20 h of incubation. At 2 h postincubation of monocytes with heat-killed C. albicans (HKCA) (2:1) to stimulate IL-12, concentrated fungal supernatant fluids were added and incubated for an additional 20 h. The present data show that, unlike supernatant fluids obtained from S. cerevisiae, the C. albicans supernatant fluids significantly suppressed IL-12 production induced by HKCA. This suggested that the inhibition is Candida specific. A preliminary biochemical analysis revealed that this secretory IL-12 inhibitory factor is glycoprotein in nature. The inhibitory activity had no effect on the phagocytosis of yeasts. Supernatant fluids from C. albicans markedly induced the phosphoryllation of ERK44/42 MAPK, but not p38 and SAPK, I min after they were added to monocytes. To test if the induction of ERK44/42 MAPK was central to the IL-12 inhibition, we used gamma interferon (IFN-gamma) (1 ng/ml) plus lipopollysaccharide (LPS) (100 ng/ml) to stimulate IL-12 production by monocytes. The inhibition of ERK MAPK by the specific inhibitor PD 98059 significantly reduced phospho-ERK44/42 MAPK levels induced by C. albicans supernatant fluids in the IFN-gamma-plus-LPS-driven monocytes. Concomitantly, PD 98059 reversed the IL-12 inhibitory activity of the C. albicans supernatant (P < 0.01). These data indicate that C. albicans can inhibit IL-12 production by secreting an ERK44/42 MAPK-stimulating factor and thus can attenuate effective immune responses.
引用
收藏
页码:2513 / 2520
页数:8
相关论文
共 27 条
[1]   Candida albicans infection enhances immuno suppression induced by cyclophosphamide by selective priming of suppressive myeloid progenitors for NO production [J].
Angulo, I ;
Jiménez-Díaz, MB ;
García-Bustos, JF ;
Gargallo, D ;
de las Heras, FG ;
Muñoz-Fernández, MA ;
Fresno, M .
CELLULAR IMMUNOLOGY, 2002, 218 (1-2) :46-58
[2]   Candida albicans induces the release of inflammatory mediators from human peripheral blood monocytes [J].
Castro, M ;
Bjoraker, JA ;
Rohrbach, MS ;
Limper, AH .
INFLAMMATION, 1996, 20 (01) :107-122
[3]   MAP kinases in the immune response [J].
Dong, C ;
Davis, RJ ;
Flavell, RA .
ANNUAL REVIEW OF IMMUNOLOGY, 2002, 20 :55-72
[4]  
Feng GJ, 1999, J IMMUNOL, V163, P6403
[5]  
Forsyth CB, 1998, J IMMUNOL, V161, P6198
[6]   Interleukin-12 production by human monocytes infected with Mycobacterium tuberculosis: Role of phagocytosis [J].
Fulton, SA ;
Johnsen, JM ;
Wolf, SF ;
Sieburth, DS ;
Boom, WH .
INFECTION AND IMMUNITY, 1996, 64 (07) :2523-2531
[7]   Transforming growth factor β1 in the presence of granulocyte/macrophage colony-stimulating factor and interleukin 4, induces differentiation of human peripheral blood monocytes into dendritic Langerhans cells [J].
Geissmann, F ;
Prost, C ;
Monnet, JP ;
Dy, M ;
Brousse, N ;
Hermine, O .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (06) :961-966
[8]   Potential role of phospholipases in virulence and fungal pathogenesis [J].
Ghannoum, MA .
CLINICAL MICROBIOLOGY REVIEWS, 2000, 13 (01) :122-+
[9]   Biochemical characterization and protein kinase C dependency of monokine-inducing activities of Toxoplasma gondii [J].
Grunvald, E ;
Chiaramonte, M ;
Hieny, S ;
Wysocka, M ;
Trinchieri, G ;
Vogel, SN ;
Gazzinelli, RT ;
Sher, A .
INFECTION AND IMMUNITY, 1996, 64 (06) :2010-2018
[10]   Activated complement component 3 (C3) is required for ultraviolet induction of immunosuppression and antigenic tolerance [J].
Hammerberg, C ;
Katiyar, SK ;
Carroll, MC ;
Cooper, KD .
JOURNAL OF EXPERIMENTAL MEDICINE, 1998, 187 (07) :1133-1138