Mesenteric fat-control site for bacterial translocation in colitis?

被引:56
作者
Batra, A. [1 ]
Heimesaat, M. M. [2 ]
Bereswill, S. [2 ]
Fischer, A. [2 ]
Glauben, R. [1 ]
Kunkel, D. [3 ,4 ]
Scheffold, A. [5 ]
Erben, U. [1 ]
Kuehl, A. [6 ]
Loddenkemper, C. [6 ]
Lehr, H-A [7 ]
Schumann, M. [1 ]
Schulzke, J-D [1 ]
Zeitz, M. [1 ]
Siegmund, B. [1 ]
机构
[1] Charite, Dept Med 1, D-13353 Berlin, Germany
[2] Charite, Inst Microbiol & Hyg, D-13353 Berlin, Germany
[3] Charite, Campus Virchow Klinikum, D-13353 Berlin, Germany
[4] Berlin Brandenburg Ctr Regenerat Therapies, Berlin, Germany
[5] Miltenyi Biotec, Bergisch Gladbach, Germany
[6] Charite, Inst Pathol, RCIS, D-13353 Berlin, Germany
[7] Univ Lausanne Hosp, Inst Pathol, Lausanne, Switzerland
关键词
EPITHELIAL BARRIER FUNCTION; INFLAMMATORY-BOWEL-DISEASE; TOLL-LIKE RECEPTORS; CROHNS-DISEASE; INTESTINAL INFLAMMATION; ADIPOSE-TISSUE; LEPTIN; MICE; HOMEOSTASIS; ADIPOCYTES;
D O I
10.1038/mi.2012.33
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
In Crohn's disease bacteria could be detected in the adjacent mesenteric fat characterized by hypertrophy of unknown function. This study aimed to define effector responses of this compartment induced by bacterial translocation during intestinal inflammation. Dextran sulfate sodium-induced colitis served as a model of intestinal inflammation. Translocation of peptides and bacteria into mesenteric fat was evaluated. Innate functions of mesenteric fat and epithelium were characterized at whole tissue, cellular, and effector molecule levels. Orally applied peptides translocated in healthy wild-type (WT) mice. Bacterial translocation was not detected in healthy and acute but increased in chronic colitis. Mesenteric fat from colitic mice released elevated levels of cytokines and was infiltrated by immune cells. In MyD88(-/-) mice bacterial translocation occurred in health and increased in colitis. The exaggerated cytokine production in mesenteric fat accompanying colonic inflammation in WT mice was less distinct in MyD88(-/-) mice. In vitro studies revealed that fat not only increases cytokine production following contact with bacterial products, but also that preadipocytes are potent phagocytes. Colonic inflammation is accompanied by massive cytokine production and immune cell infiltration in adjacent adipose tissue. These effects can be considered as protective mechanisms of the mesenteric fat in the defense of bacterial translocation.
引用
收藏
页码:580 / 591
页数:12
相关论文
共 50 条
  • [11] Visceral fat adipokine secretion is associated with systemic inflammation in obese humans
    Fontana, Luigi
    Eagon, J. Christopher
    Trujillo, Maria E.
    Scherer, Philipp E.
    Klein, Samuel
    [J]. DIABETES, 2007, 56 (04) : 1010 - 1013
  • [12] High-Resolution Analysis of Barrier Function
    Fromm, Michael
    Krug, Susanne M.
    Zeissig, Sebastian
    Richter, Jan E.
    Rosenthal, Rita
    Schulzke, Joerg-Dieter
    Guenzel, Dorothee
    [J]. MOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS, 2009, 1165 : 74 - 81
  • [13] Gay J, 2005, GASTROENTEROLOGY, V128, pA503
  • [14] MyD88 signalling plays a critical role in host defence by controlling pathogen burden and promoting epithelial cell homeostasis during Citrobacter rodentium-induced colitis
    Gibson, D. L.
    Ma, C.
    Bergstrom, K. S. B.
    Huang, J. T.
    Man, C.
    Vallance, B. A.
    [J]. CELLULAR MICROBIOLOGY, 2008, 10 (03) : 618 - 631
  • [15] Shift Towards Pro-inflammatory Intestinal Bacteria Aggravates Acute Murine Colitis via Toll-like Receptors 2 and 4
    Heimesaat, Markus M.
    Fischer, Andre
    Siegmund, Britta
    Kupz, Andreas
    Niebergall, Julia
    Fuchs, David
    Jahn, Hannah-Katharina
    Freudenberg, Marina
    Loddenkemper, Christoph
    Batra, Arvind
    Lehr, Hans-Anton
    Liesenfeld, Oliver
    Blaut, Michael
    Goebel, Ulf B.
    Schumann, Ralf R.
    Bereswill, Stefan
    [J]. PLOS ONE, 2007, 2 (07):
  • [16] Unresponsiveness of MyD88-deficient mice to endotoxin
    Kawai, T
    Adachi, O
    Ogawa, T
    Takeda, K
    Akira, S
    [J]. IMMUNITY, 1999, 11 (01) : 115 - 122
  • [17] Interleukin-6: discovery of a pleiotropic cytokine
    Kishimoto, Tadamitsu
    [J]. ARTHRITIS RESEARCH & THERAPY, 2006, 8 (Suppl 2)
  • [18] Th1-type responses mediate spontaneous ileitis in a novel murine model of Crohn's disease
    Kosiewicz, MM
    Nast, CC
    Krishnan, A
    Rivera-Nieves, J
    Moskaluk, CA
    Matsumoto, S
    Kozaiwa, K
    Cominelli, F
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 2001, 107 (06) : 695 - 702
  • [19] Visualization of peptide presentation following oral application of antigen in normal and Peyer's patches-deficient mice
    Kunkel, D
    Kirchhoff, D
    Nishikawa, SI
    Radbruch, A
    Scheffold, A
    [J]. EUROPEAN JOURNAL OF IMMUNOLOGY, 2003, 33 (05) : 1292 - 1301
  • [20] Sensitive visualization of peptide presentation in vitro and ex vivo
    Kunkel, S
    Kirchhoff, D
    Volkmer-Engert, R
    Radbruch, A
    Scheffold, A
    [J]. CYTOMETRY PART A, 2003, 54A (01): : 19 - 26