Intestinal innate immunity to Campylobacter jejuni results in induction of bactericidal human beta-defensins 2 and 3

被引:70
作者
Zilbauer, M
Dorrell, N
Boughan, PK
Harris, A
Wren, BW
Klein, NJ
Bajaj-Elliott, M
机构
[1] Inst Child Hlth, Dept Microbiol & Infect Dis, London WC1N 1EH, England
[2] London Sch Hyg & Trop Med, Dept Infect & Trop Dis, London WC1, England
[3] Barts & London Queen Marys Sch Med & Dent, Inst Cell & Mol Sci, MRC, Mol Pathogenesis Ctr Infect Dis, London, England
关键词
D O I
10.1128/IAI.73.11.7281-7289.2005
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Campylobacter jejuni is the most prevalent cause of bacterial diarrhea worldwide. Despite the serious health problems caused by this bacterium, human innate immune responses to C. jejuni infection remain poorly defined. Human beta-defensins, a family of epithelial antimicrobial peptides, are a major component of host innate defense at the gastrointestinal mucosal surface. In this study, the effect of two different C. jejuni wild-type strains on human intestinal epithelial innate responses was investigated. Up-regulation of P-defensin gene and peptide expression during infection was observed and recombinant beta-defensins were shown to have a direct bactericidal effect against C. jejuni through disruption of cell wall integrity. Further studies using an isogenic capsule-deficient mutant showed that, surprisingly, the absence of the bacterial polysaccharide capsule did not change the innate immune responses induced by C jejuni or the ability of C. jejuni to survive exposure to recombinant beta-defensins. This study suggests a major role for this family of antimicrobial peptides in the innate immune defense against this human pathogen.
引用
收藏
页码:7281 / 7289
页数:9
相关论文
共 41 条
[31]   The biochemistry and genetics of capsular polysaccharide production in bacteria [J].
Roberts, IS .
ANNUAL REVIEW OF MICROBIOLOGY, 1996, 50 :285-315
[32]   Protection against enteric salmonellosis in transgenic mice expressing a human intestinal defensin [J].
Salzman, NH ;
Ghosh, D ;
Huttner, KM ;
Paterson, Y ;
Bevins, CL .
NATURE, 2003, 422 (6931) :522-526
[33]   Sequential spread of Campylobacter infection in a multipen broiler house [J].
Shreeve, JE ;
Toszeghy, M ;
Pattison, M ;
Newell, DG .
AVIAN DISEASES, 2000, 44 (04) :983-988
[34]   Differential regulation of β-defensin expression in human skin by microbial stimuli [J].
Sorensen, OE ;
Thapa, DR ;
Rosenthal, A ;
Liu, LD ;
Roberts, AA ;
Ganz, T .
JOURNAL OF IMMUNOLOGY, 2005, 174 (08) :4870-4879
[35]   Emerging foodborne diseases: An evolving public health challenge [J].
Tauxe, RV .
EMERGING INFECTIOUS DISEASES, 1997, 3 (04) :425-434
[36]   Pathophysiology of Campylobacter jejuni infections of humans [J].
Wassenaar, TM ;
Blaser, MJ .
MICROBES AND INFECTION, 1999, 1 (12) :1023-1033
[37]   NOD2 (CARD15) mutations in Crohn's disease are associated with diminished mucosal α-defensin expression [J].
Wehkamp, J ;
Harder, J ;
Weichenthal, M ;
Schwab, M ;
Schäffeler, E ;
Schlee, M ;
Herrlinger, KR ;
Stallmach, A ;
Noack, F ;
Fritz, P ;
Schröder, JM ;
Bevins, CL ;
Fellermann, K ;
Stange, EF .
GUT, 2004, 53 (11) :1658-1664
[38]   Inducible and constitutive β-defensins are differentially expressed in Crohn's disease and ulcerative colitis [J].
Wehkamp, J ;
Harder, J ;
Weichenthal, M ;
Mueller, O ;
Herrlinger, KR ;
Fellermann, K ;
Schroeder, JM ;
Stange, EF .
INFLAMMATORY BOWEL DISEASES, 2003, 9 (04) :215-223
[39]   Defensin pattern in chronic gastritis:: HBD-2 is differentially expressed with respect to Helicobacter pylori status [J].
Wehkamp, J ;
Schmidt, K ;
Herrlinger, KR ;
Baxmann, S ;
Behling, S ;
Wohlschläger, C ;
Feller, AC ;
Stange, EF ;
Fellermann, K .
JOURNAL OF CLINICAL PATHOLOGY, 2003, 56 (05) :352-357
[40]   Mechanisms of antimicrobial peptide action and resistance [J].
Yeaman, MR ;
Yount, NY .
PHARMACOLOGICAL REVIEWS, 2003, 55 (01) :27-55