Listeria monocytogenes modulates macrophage cytokine responses through STAT serine phosphorylation and the induction of suppressor of cytokine signaling 3

被引:79
作者
Stoiber, D
Stockinger, S
Steinlein, P
Kovarik, J
Decker, T
机构
[1] Vienna Bioctr, Inst Microbiol & Genet, A-1030 Vienna, Austria
[2] Vienna Bioctr, Inst Mol Pathol, A-1030 Vienna, Austria
[3] Masaryk Mem Canc Inst, Dept Cellular & Mol Oncol, Brno, Czech Republic
关键词
D O I
10.4049/jimmunol.166.1.466
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Macrophage activation as part of natural resistance to infection is caused by stimulation with IFN-gamma and by the invading microorganisms or microbial products. Infection of macrophages with the Gram-positive bacterium Listeria monocytogenes for short periods before activation with IFN-gamma increased the phosphorylation of transcription factor STAT1 at S727 and thereby the expression of IFN-gamma -induced genes. By contrast, persistent infection with viable bacteria or treatment with heat-killed Listeria diminished IFN-gamma -stimulated transcription and the phosphorylation of STAT1 at Y701. Decreased IFN-gamma signaling correlated with the induction of suppressor of cytokine signaling 3 (SOCS3) mRNA and protein. Contrasting our previous findings with LPS, maximal synthesis of SOCS3 required both the immediate signals from Listeria receptors on the cell surface and the activity of a polypeptide secreted in response to bacterial infection, SOCS3 induction by the secreted protein could not be blocked by neutralizing Abs to IL-10 and it did not require the presence of STAT1, Consistent with the induction of SOCS3 activity, Listeria also inhibited activation of STAT5 by GM-CSF, The p38 mitogen-activated protein kinase was rapidly activated upon infection of macrophages with L, monocytogenes, Inhibition of p38 mitogen-activated protein kinase with the pyridinyl imidazol SB203580 abrogated both STAT1 S727 phosphorylation and the expression of SOCS3, The data suggest that STAT1 serine kinase and SOCS3 activity are hallmarks of immediate and delayed phases of influence by bacterial signals on signal transduction in response to IFN-gamma.
引用
收藏
页码:466 / 472
页数:7
相关论文
共 53 条
[1]  
Alleva DG, 1997, J IMMUNOL, V159, P2941
[2]  
BACCARINI M, 1985, J IMMUNOL, V134, P2658
[3]   NF-kappa B: Ten years after [J].
Baeuerle, PA ;
Baltimore, D .
CELL, 1996, 87 (01) :13-20
[4]   BACILLUS-SUBTILIS EXPRESSING A HEMOLYSIN GENE FROM LISTERIA-MONOCYTOGENES CAN GROW IN MAMMALIAN-CELLS [J].
BIELECKI, J ;
YOUNGMAN, P ;
CONNELLY, P ;
PORTNOY, DA .
NATURE, 1990, 345 (6271) :175-176
[5]   LPS and TNFα induce SOCS3 mRNA and inhibit IL-6-induced activation of STAT3 in macrophages [J].
Bode, JG ;
Nimmesgern, A ;
Schmitz, J ;
Schaper, F ;
Schmitt, M ;
Frisch, W ;
Hussinger, D ;
Heinrich, PC ;
Graeve, L .
FEBS LETTERS, 1999, 463 (03) :365-370
[6]   Interactions of Listeria monocytogenes with mammalian cells during entry and actin-based movement:: bacterial factors, cellular ligands and signaling [J].
Cossart, P ;
Lecuit, M .
EMBO JOURNAL, 1998, 17 (14) :3797-3806
[7]   SB-203580 IS A SPECIFIC INHIBITOR OF A MAP KINASE HOMOLOG WHICH IS STIMULATED BY CELLULAR STRESSES AND INTERLEUKIN-1 [J].
CUENDA, A ;
ROUSE, J ;
DOZA, YN ;
MEIER, R ;
COHEN, P ;
GALLAGHER, TF ;
YOUNG, PR ;
LEE, JC .
FEBS LETTERS, 1995, 364 (02) :229-233
[8]  
DAMELL JE, 1994, SCIENCE, V264, P1415
[9]   Serine phosphorylation of STATs [J].
Decker, T ;
Kovarik, P .
ONCOGENE, 2000, 19 (21) :2628-2637
[10]   GAS elements: A few nucleotides with a major impact on cytokine-induced gene expression [J].
Decker, T ;
Kovarik, P ;
Meinke, A .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 1997, 17 (03) :121-134