Helicobacter infection:: pathogenesis

被引:21
作者
Blanchard, TG [1 ]
Drakes, ML [1 ]
Czinn, SJ [1 ]
机构
[1] Case Western Reserve Univ, Sch Med, Dept Pediat, Cleveland, OH 44106 USA
关键词
Helicobacter pylori; pathogenesis; infection; CagA;
D O I
10.1097/00001574-200401000-00004
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Purpose of review Helicobacter pylori remains one of the world's most prevalent bacterial pathogens, often causing gastritis, peptic ulcer disease, gastric mucosa-associated lymphatic tissue lymphoma, or gastric adenocarcinoma. Elucidation of H. pylori virulence mechanisms and characteristics of the host that contribute to pathogenesis will facilitate the development of both pharmacologic and immunologic therapies. Recent findings The functional status of the outer inflammatory protein A may have predictive value for duodenal ulcer, and host alleles for interleukin-1beta, interleukin-1R, tumor necrosis factor-a, and interleukin-10 correlate with increased risk for gastric cancer. H. pylori vacuolating cytotoxin A and cytotoxin-associated gene A protein interact with multiple host proteins, although downstream signaling events need further characterization. It does appear however, that CagA may participate in a negative feedback loop on Src family kinases to prevent further phosphorylation of CagA. Several models, including delayed type hypersensitivity in immune mice, and spontaneous clearance of H. pylori from interleukin-10(-/-) and phagocyte oxidase(-/-) mice, provide evidence that severe inflammation may be sufficient to eradicate H. pylori. The strategies used by H. pylori to avoid the inflammatory response are also becoming clearer. H. pylori remains viable when internalized by epithelial cells, and it remains viable in macrophage phagosomes by inhibiting phagosome maturation. Additionally, H. pylori may regulate the host immune response through activation of dendritic cells and CD25(+) regulatory T cells, and it may direct immunosuppression of T cells. Summary Helicobacter pylori virulence is accomplished through many mechanisms, including vacuolating cytotoxin A and CagA activities, and may be predicted based on bacterial and host genotypes. Ultimately, H. pylori persistence may depend on its success in downregulating the inflammatory response.
引用
收藏
页码:10 / 15
页数:6
相关论文
共 45 条
[1]   Protection against Helicobacter pylori infection following immunization is IL-12-dependent and mediated by Th1 cells [J].
Akhiani, AA ;
Pappo, J ;
Kabok, Z ;
Schön, K ;
Gao, W ;
Franzén, LE ;
Lycke, N .
JOURNAL OF IMMUNOLOGY, 2002, 169 (12) :6977-6984
[2]   Virulent strains of Helicobacter pylori demonstrate delayed phagocytosis and stimulate homotypic phagosome fusion in macrophages [J].
Allen, LAH ;
Schlesinger, LS ;
Kang, B .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 191 (01) :115-127
[3]   Disruption of the epithelial apical-junctional complex by Helicobacter pylori CagA [J].
Amieva, MR ;
Vogelmann, R ;
Covacci, A ;
Tompkins, LS ;
Nelson, WJ ;
Falkow, S .
SCIENCE, 2003, 300 (5624) :1430-1434
[4]   Helicobacter pylori enter and survive within multivesicular vacuoles of epithelial cells [J].
Amieva, MR ;
Salama, NR ;
Tompkins, LS ;
Falkow, S .
CELLULAR MICROBIOLOGY, 2002, 4 (10) :677-690
[5]   Cutting edge: Carbohydrate profiling identifies new pathogens that interact with dendritic cell-specific ICAM-3-grabbing nonintegrin on dendritic cells [J].
Appelmelk, BJ ;
van Die, I ;
van Vliet, SJ ;
Vandenbroucke-Grauls, CMJE ;
Geijtenbeek, TBH ;
van Kooyk, Y .
JOURNAL OF IMMUNOLOGY, 2003, 170 (04) :1635-1639
[6]  
Bäckhed F, 2003, J INFECT DIS, V187, P829
[7]   Mitogen-activated protein kinases and nuclear factor-κB regulate Helicobacter pylori-mediated interleukin-8 release from macrophages [J].
Bhattacharyya, A ;
Pathak, S ;
Datta, S ;
Chattopadhyay, S ;
Basu, J ;
Kundu, M .
BIOCHEMICAL JOURNAL, 2002, 368 :121-129
[8]   Severe inflammation and reduced bacteria load in murine Helicobacter infection caused by lack of phagocyte oxidase activity [J].
Blanchard, TG ;
Yu, FW ;
Hsieh, CL ;
Redline, RW .
JOURNAL OF INFECTIOUS DISEASES, 2003, 187 (10) :1609-1615
[9]   Reduced colonization of gastric mucosa by Helicobacter pylori in mice deficient in interleukin-10 [J].
Chen, WX ;
Shu, DR ;
Chadwick, VS .
JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, 2001, 16 (04) :377-383
[10]   Helicobacter pylori CagA protein targets the c-Met receptor and enhances the motogenic response [J].
Churin, Y ;
Al-Ghoul, L ;
Kepp, O ;
Meyer, TE ;
Birchmeier, W ;
Naumann, M .
JOURNAL OF CELL BIOLOGY, 2003, 161 (02) :249-255