Chronic Intestinal Inflammation Induces Stress-Response Genes in Commensal Escherichia coli

被引:67
作者
Patwa, Laura G. [1 ,2 ]
Fan, Ting-Jia [1 ,2 ]
Tchaptchet, Sandrine [1 ,2 ]
Liu, Yang [3 ,4 ,5 ,6 ]
Lussier, Yves A. [3 ,4 ,5 ,6 ]
Sartor, R. Balfour [1 ,2 ,7 ]
Hansen, Jonathan J. [1 ,2 ]
机构
[1] Univ N Carolina, Dept Med, Div Gastroenterol & Hepatol, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Ctr Gastrointestinal Biol & Dis, Chapel Hill, NC 27599 USA
[3] Univ Chicago, Dept Med, Ctr Biomed Informat, Chicago, IL 60637 USA
[4] Univ Chicago, Med Genet Sect, Chicago, IL 60637 USA
[5] Univ Chicago, Inst Genom & Syst Biol, Chicago, IL 60637 USA
[6] Univ Chicago, Inst Translat Med, Chicago, IL 60637 USA
[7] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC 27599 USA
关键词
IFN; Gene Expression Profiling; Mouse Model; IBD; Microbiota; HEAT-SHOCK PROTEINS; CROHNS-DISEASE; OXIDATIVE STRESS; HIGH PREVALENCE; BOWEL DISEASES; ILEAL MUCOSA; IN-VIVO; BACTERIA; IBPB; MICE;
D O I
10.1053/j.gastro.2011.06.064
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Intestinal microbes induce homeostatic mucosal immune responses, but can also cause inappropriate immune activation in genetically susceptible hosts. Although immune responses to bacterial products have been studied extensively, little is known about how intestinal inflammation affects functions of commensal luminal microbes. METHODS: Microarrays and real-time polymerase chain reaction were used to profile transcriptional changes in luminal bacteria from wild-type and IL-10(-/-) mice monoassociated with a nonpathogenic, murine isolate of Escherichia coli (NC101, which causes colitis in gnotobiotic IL-10(-/-) mice). Colonic inflammation and innate and adaptive immune responses were measured in wild-type and IL-10(-/-) mice monoassociated with mutant NC101 that lack selected, up-regulated genes, and in IL-10(-/-) mice that were colonized with a combination of mutant and parental NC101. We measured intracellular survival of bacteria within primary macrophages from mice and resulting production of tumor necrosis factor. RESULTS: Bacteria from IL-10(-/-) mice with colitis had significant up-regulation of the stress-response regulon, including the small heat shock proteins IbpA and IbpB that protect E coli from oxidative stress, compared to healthy, wild-type controls. In IL10(-/-) mice, expression of ibpAB reduced histologic signs of colon inflammation, secretion of interleukin-12/23p40 in colonic explant cultures, serologic reactivity to NC101 antigens, and secretion of interferon-gamma by stimulated mesenteric lymph node cells. Infection of primary macrophages by bacteria that express ibpAB was associated with decreased intracellular survival and reduced secretion of tumor necrosis factor. CONCLUSIONS: Chronic intestinal inflammation causes functional alterations in gene expression in commensal gut bacterium (E coli NC101). Further studies of these expression patterns might identify therapeutic targets for patients with inflammatory bowel diseases.
引用
收藏
页码:1842 / U411
页数:20
相关论文
共 37 条
[1]   A small, stable RNA induced by oxidative stress: Role as a pleiotropic regulator and antimutator [J].
Altuvia, S ;
WeinsteinFischer, D ;
Zhang, AX ;
Postow, L ;
Storz, G .
CELL, 1997, 90 (01) :43-53
[2]   Sero-reactivity to microbial components in Crohn's disease is associated with disease severity and progression, but not NOD2/CARD15 genotype [J].
Arnott, IDR ;
Landers, CJ ;
Nimmo, EJ ;
Drummond, HE ;
Smith, BKR ;
Targan, SR ;
Satsangi, J .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2004, 99 (12) :2376-2384
[3]   GO::TermFinder - open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes [J].
Boyle, EI ;
Weng, SA ;
Gollub, J ;
Jin, H ;
Botstein, D ;
Cherry, JM ;
Sherlock, G .
BIOINFORMATICS, 2004, 20 (18) :3710-3715
[4]   The Gene Ontology Annotation (GOA) Database: sharing knowledge in Uniprot with Gene Ontology [J].
Camon, E ;
Magrane, M ;
Barrell, D ;
Lee, V ;
Dimmer, E ;
Maslen, J ;
Binns, D ;
Harte, N ;
Lopez, R ;
Apweiler, R .
NUCLEIC ACIDS RESEARCH, 2004, 32 :D262-D266
[5]   Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis [J].
Carroll, Ian M. ;
Andrus, Jason M. ;
Bruno-Barcena, Jose M. ;
Klaenhammer, Todd R. ;
Hassan, Hosni M. ;
Threadgill, Deborah S. .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2007, 293 (04) :G729-G738
[6]   Presence of adherent Escherichia coli strains in ileal mucosa of patients with Crohn's disease [J].
Darfeuille-Michaud, A ;
Neut, C ;
Barnich, N ;
Lederman, E ;
Di Martino, P ;
Desreumaux, P ;
Gambiez, L ;
Joly, B ;
Cortot, A ;
Colombel, JF .
GASTROENTEROLOGY, 1998, 115 (06) :1405-1413
[7]   High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease [J].
Darfeuille-Michaud, A ;
Boudeau, J ;
Bulois, P ;
Neut, C ;
Glasser, AL ;
Barnich, N ;
Bringer, MA ;
Swidsinski, A ;
Beaugerie, L ;
Colombel, JF .
GASTROENTEROLOGY, 2004, 127 (02) :412-421
[8]   One-step inactivation of chromosomal genes in Escherichia coli K-12 using PCR products [J].
Datsenko, KA ;
Wanner, BL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (12) :6640-6645
[9]  
Davidson NJ, 1998, J IMMUNOL, V161, P3143
[10]   Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases [J].
Frank, Daniel N. ;
Amand, Allison L. St. ;
Feldman, Robert A. ;
Boedeker, Edgar C. ;
Harpaz, Noam ;
Pace, Norman R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (34) :13780-13785