TLR signaling in the gut in health and disease

被引:458
作者
Abreu, MT
Fukata, M
Arditi, M
机构
[1] Mt Sinai Sch Med, Ctr Inflammatory Bowel Dis, Div Gastroenterol, Dept Med, New York, NY 10029 USA
[2] Cedars Sinai Med Ctr, Burns & Allen Res Inst, Steven Spielberg Pediat Res Ctr, Div Pediat Infect Dis,Dept Pediat, Los Angeles, CA 90048 USA
关键词
D O I
10.4049/jimmunol.174.8.4453
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
The human intestine has evolved in the presence of diverse enteric microflora. TLRs convert the recognition of pathogen-associated molecules in the gut into signals for antimicrobial peptide expression, barrier fortification, and proliferation of epithelial cells. Healing of injured intestinal epithelium and clearance of intramucosal bacteria require the presence of intact TLR signaling. Nucleotide oligomerization domain (Nod)1 and Nod2 are additional pattern recognition receptors that are required for defense against invasive enteric pathogens. Through spatial and functional localization of TLR and Nod molecules, the normal gut maintains a state of controlled inflammation. By contrast, patients with inflammatory bowel disease demonstrate inflammation in response to the normal flora. A subset of these patients carry polymorphisms in TLR and CARD15/NOD2 genes. A better understanding of the delicate regulation of TLR and Nod molecules in the gut may lead to improved treatment for enteric infections and idiopathic inflammatory bowel diseases.
引用
收藏
页码:4453 / 4460
页数:8
相关论文
共 105 条
[1]  
ABRAMS GD, 1963, LAB INVEST, V12, P355
[2]   TLR4 and MD-2 expression is regulated by immune-mediated signals in human intestinal epithelial cells [J].
Abreu, MT ;
Arnold, ET ;
Thomas, LS ;
Gonsky, R ;
Zhou, YH ;
Hu, B ;
Arditi, M .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (23) :20431-20437
[3]   Decreased expression of toll-like receptor-4 and MD-2 correlates with intestinal epithelial cell protection against dysregulated proinflammatory gene expression in response to bacterial lipopolysaccharide [J].
Abreu, MT ;
Vora, P ;
Faure, E ;
Thomas, LS ;
Arnold, ET ;
Arditi, M .
JOURNAL OF IMMUNOLOGY, 2001, 167 (03) :1609-1616
[4]   Bacterial DNA evokes epithelial IL-8 production by a MAPK-dependent, NFκB-independent pathway [J].
Akhtar, M ;
Watson, JL ;
Nazli, A ;
McKay, DM .
FASEB JOURNAL, 2003, 17 (08) :1319-+
[5]   Innate immunity via Toll-like receptors and Nod proteins [J].
Athman, R ;
Philpott, D .
CURRENT OPINION IN MICROBIOLOGY, 2004, 7 (01) :25-32
[6]   Secretion of microbicidal α-defensins by intestinal Paneth cells in response to bacteria [J].
Ayabe, T ;
Satchell, DP ;
Wilson, CL ;
Parks, WC ;
Selsted, ME ;
Ouellette, AJ .
NATURE IMMUNOLOGY, 2000, 1 (02) :113-118
[7]   In vitro and ex vivo activation of the TLR5 signaling pathway in intestinal epithelial cells by a commensal Escherichia coli strain [J].
Bambou, JC ;
Giraud, A ;
Menard, S ;
Begue, B ;
Rakotobe, S ;
Heyman, M ;
Taddei, FO ;
Cerf-Bensussan, N ;
Gaboriau-Routhiau, V .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (41) :42984-42992
[8]   Toll-like receptor 4 signaling by intestinal microbes influences susceptibility to food allergy [J].
Bashir, MEH ;
Louie, S ;
Shi, HN ;
Nagler-Anderson, C .
JOURNAL OF IMMUNOLOGY, 2004, 172 (11) :6978-6987
[9]   TLRs govern neutrophil activity in aspergillosis [J].
Bellocchio, S ;
Moretti, S ;
Perruccio, K ;
Fallarino, F ;
Bozza, S ;
Montagnoli, C ;
Mosci, P ;
Lipford, GB ;
Pitzurra, L ;
Romani, L .
JOURNAL OF IMMUNOLOGY, 2004, 173 (12) :7406-7415
[10]   Weighted walkthroughs between extended entities for retrieval by spatial arrangement [J].
Berretti, S ;
Del Bimbo, A ;
Vicario, E .
IEEE TRANSACTIONS ON MULTIMEDIA, 2003, 5 (01) :52-70