Inhibition of heat shock protein expression by Helicobacter pylori.
Heat shock proteins (HSPs) are primarily known as molecular chaperones that are induced by cell stress and prevent protein aggregation and facilitate folding. Recent evidence suggests that exposure of cells to microbial pathogens can also induce HSPs, which then modulate both innate and adaptive immune responses. Paradoxically, Helicobacter pylori has been found to decrease expression of HSPs. We sought to investigate this phenomenon further and to examine the role of different H. pylori strains and recognized virulence factors in cell culture and in the mouse model. Co-culture of H. pylori with two gastric carcinoma cell lines reduced expression of HSP70 and, to a lesser extent, HSP60. Down modulation of HSPs was not dependent on the presence of the vacuolating cytotoxin (VacA) or the cag pathogenicity island (cag PAI). C57BL/6 mice infected with a human H. pylori strain also demonstrated reduced expression of HSP70, HSP8, and heat shock factor 1 (HSF-1), a transcriptional activator of HSP70. In contrast, the bacterial pathogen, S. Typhimurium up-regulated HSP expression. Since HSPs are thought to function as danger signals during microbial infection, H. pylori down-regulation of HSPs may be a mechanism of immune evasion that promotes chronic infection.
Axsen
Wendy S
WS
Center for Comparative Medicine, University of California, Davis, CA 95616, USA.
Styer
Cathy M
CM
Solnick
Jay V
JV
D000818:Animals; D045744:Cell Line, Tumor; D018834:Chaperonin 60 / Q000096:biosynthesis*; D018920:Coculture Techniques; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D015536:Down-Regulation; D004847:Epithelial Cells / Q000382:microbiology; D005260:Female; D050886:HSP20 Heat-Shock Proteins / Q000096:biosynthesis; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; D016480:Helicobacter pylori / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018832:Molecular Chaperones; D009124:Muscle Proteins / Q000096:biosynthesis; D012486:Salmonella typhimurium / Q000472:pathogenicity; D014157:Transcription Factors / Q000096:biosynthesis
D018834:Chaperonin 60; D004268:DNA-Binding Proteins; D050886:HSP20 Heat-Shock Proteins; D018840:HSP70 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C490017:Hsf1 protein, mouse; C490206:Hspb8 protein, mouse; D018832:Molecular Chaperones; D009124:Muscle Proteins; D014157:Transcription Factors
J Physiol Pharmacol. 2001 Mar;52(1):153-64
11321509
Lancet. 2003 Aug 9;362(9382):469-76
12927437
Infect Immun. 2005 Jun;73(6):3358-66
15908362
Gut. 2001 May;48(5):598-604
11302954
Science. 2002 Apr 12;296(5566):301-5
11951032
Clin Microbiol Rev. 2006 Jul;19(3):449-90
16847081
Nat Rev Microbiol. 2005 Apr;3(4):320-32
15759043
Infect Immun. 2001 Nov;69(11):6887-92
11598063
Proc Natl Acad Sci U S A. 2003 Mar 18;100(6):3467-72
12629225
Proteomics. 2004 Nov;4(11):3335-42
15378740
Stem Cells. 2005 Nov-Dec;23(10):1502-13
16100000
Cell Stress Chaperones. 2003 Summer;8(2):194-203
14627205
Trends Immunol. 2002 Mar;23(3):130-5
11864840
Clin Exp Immunol. 2006 Jul;145(1):183-9
16792689
Infect Immun. 2001 Nov;69(11):6970-80
11598072
Gastroenterology. 2008 Apr;134(4):1049-57
18395086
J Physiol Pharmacol. 2006 Jun;57(2):265-78
16845230
Proc Natl Acad Sci U S A. 1998 Oct 13;95(21):12619-24
9770535
Gastroenterology. 1998 Feb;114(2):245-55
9453483
Nat Rev Immunol. 2005 Apr;5(4):318-30
15803151
J Leukoc Biol. 2004 Sep;76(3):514-9
15178705
Clin Microbiol Rev. 2006 Oct;19(4):597-613
17041136
J Biol Chem. 1996 Oct 4;271(40):24874-9
8926278
Infect Immun. 2006 Jul;74(7):3693-706
16790742
J Bacteriol. 1993 Sep;175(18):5899-906
8376337
Cell Stress Chaperones. 1998 Dec;3(4):221-7
9880234
Am J Obstet Gynecol. 1999 Mar;180(3 Pt 1):524-9
10076122
Am J Physiol Cell Physiol. 2004 Apr;286(4):C739-44
15001423
Science. 1993 Mar 5;259(5100):1409-10
8451637
Am J Obstet Gynecol. 2005 Mar;192(3):916-21
15746691
N Engl J Med. 2002 Oct 10;347(15):1175-86
12374879
Nat Med. 2003 Dec;9(12):1469-76
14625545
Cell Microbiol. 2005 Jul;7(7):911-9
15953024
Nature. 1999 Jan 14;397(6715):176-80
9923682
Biochem Biophys Res Commun. 2001 Aug 24;286(3):433-42
11511077
J Immunol. 2000 May 15;164(10):5416-23
10799907
Nat Med. 2000 Apr;6(4):435-42
10742151
Infect Immun. 2004 Sep;72(9):5216-26
15322016
Proc Natl Acad Sci U S A. 2002 Nov 12;99(23):15136-41
12411577
J Biol Chem. 2002 Apr 26;277(17):15028-34
11836257