title: Control of neutrophil inflammation at mucosal surfaces by secreted epithelial products.
abstract: The human intestine is a large and delicately balanced organ, responsible for efficiently absorbing nutrients and selectively eliminating disease-causing pathogens. The gut architecture consists of a single layer of epithelial cells that forms a barrier against the food antigens and resident microbiota within the lumen. This barrier is augmented by a thick layer of mucus on the luminal side and an underlying lamina propria containing a resident population of immune cells. Attempted breaches of the intestinal barrier by pathogenic bacteria result in the rapid induction of a coordinated innate immune response that includes release of antimicrobial peptides, activation of pattern recognition receptors, and recruitment of various immune cells. In recent years, the role of epithelial cells in initiating this immune response has been increasingly appreciated. In particular, epithelial cells are responsible for the release of a variety of factors that attract neutrophils, the body's trained bacterial killers. In this review we will highlight recent research that details a new understanding of how epithelial cells directionally secrete specific compounds at distinct stages of the inflammatory response in order to coordinate the immune response to intestinal microbes. In addition to their importance during the response to infection, evidence suggests that dysregulation of these pathways may contribute to pathologic inflammation during inflammatory bowel disease. Therefore, a continued understanding of the mechanisms by which epithelial cells control neutrophil migration into the intestine will have tremendous benefits in both the understanding of biological processes and the identification of potential therapeutic targets.
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School , Worcester, MA , USA.
authors.forename: Rose L
authors.initials: RL
authors.lastname: Szabady
authors.forename: Beth A
authors.initials: BA
authors.lastname: McCormick
keywords: MRP2; Salmonella; eicosanoids; hepoxilin; intestinal inflammation; lipid chemoattractant; lipoxygenase; neutrophil migration
references.citation: Chem Rev. 2011 Oct 12;111(10):5922-43
references.pmid: 21766791
references.citation: Nat Rev Immunol. 2013 Mar;13(3):159-75
references.pmid: 23435331
references.citation: Nat Rev Microbiol. 2012 Oct;10(10):717-25
references.pmid: 22941505
references.citation: Eur J Immunol. 2005 Aug;35(8):2486-95
references.pmid: 16025565
references.citation: Immunity. 2007 Apr;26(4):477-489
references.pmid: 17442598
references.citation: Infect Immun. 2008 Aug;76(8):3614-27
references.pmid: 18505810
references.citation: Am J Physiol Gastrointest Liver Physiol. 2004 Jun;286(6):G1024-31
references.pmid: 14739142
references.citation: Nat Rev Immunol. 2006 Mar;6(3):173-82
references.pmid: 16498448
references.citation: Nat Rev Immunol. 2003 Nov;3(11):867-78
references.pmid: 14668803
references.citation: J Cell Biol. 1996 Feb;132(3):437-50
references.pmid: 8636220
references.citation: J Leukoc Biol. 2012 Feb;91(2):207-15
references.pmid: 22058421
references.citation: FEBS J. 2006 Oct;273(19):4377-89
references.pmid: 16956372
references.citation: Am J Physiol Lung Cell Mol Physiol. 2011 Feb;300(2):L286-94
references.pmid: 21097525
references.citation: J Immunol. 2008 Dec 1;181(11):8044-52
references.pmid: 19017997
references.citation: J Immunol. 2003 Mar 1;170(5):2688-94
references.pmid: 12594298
references.citation: J Immunol. 2004 Nov 1;173(9):5712-20
references.pmid: 15494523
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Apr;280(4):G746-54
references.pmid: 11254502
references.citation: Clin Immunol. 2008 Feb;126(2):155-64
references.pmid: 18037347
references.citation: Arterioscler Thromb Vasc Biol. 2012 Aug;32(8):1970-8
references.pmid: 22499990
references.citation: Science. 2010 Oct 15;330(6002):390-393
references.pmid: 20947770
references.citation: J Cell Biol. 1997 Dec 1;139(5):1349-60
references.pmid: 9382879
references.citation: Proc Natl Acad Sci U S A. 2004 May 11;101(19):7421-6
references.pmid: 15123795
references.citation: J Biol Chem. 1993 Jun 15;268(17):12764-74
references.pmid: 7685350
references.citation: J Clin Invest. 2002 May;109(10):1373-80
references.pmid: 12021253
references.citation: J Clin Invest. 1991 Nov;88(5):1605-12
references.pmid: 1682344
references.citation: Am J Respir Cell Mol Biol. 1992 Jul;7(1):112-7
references.pmid: 1320901
references.citation: Gastroenterology. 1997 Nov;113(5):1489-500
references.pmid: 9352851
references.citation: J Immunol. 1998 Jan 1;160(1):455-66
references.pmid: 9552004
references.citation: Am J Hematol. 1998 Jan;57(1):7-15
references.pmid: 9423810
references.citation: Immunology. 1996 Dec;89(4):563-8
references.pmid: 9014822
references.citation: Mucosal Immunol. 2012 Jul;5(4):354-66
references.pmid: 22491176
references.citation: Gut. 2005 Nov;54(11):1565-72
references.pmid: 15987794
references.citation: Science. 2004 Mar 5;303(5663):1532-5
references.pmid: 15001782
references.citation: Biochem J. 1990 Feb 15;266(1):63-8
references.pmid: 2106877
references.citation: J Infect Dis. 2012 Sep 1;206(5):714-22
references.pmid: 22723643
references.citation: Cell Microbiol. 2012 Jan;14(1):120-32
references.pmid: 21951973
references.citation: Proc Natl Acad Sci U S A. 2000 Oct 24;97(22):12283-8
references.pmid: 11050248
references.citation: Nat Med. 2012 Sep;18(9):1386-93
references.pmid: 22922410
references.citation: Prostaglandins Leukot Essent Fatty Acids. 2005 Sep-Oct;73(3-4):163-77
references.pmid: 16125378
references.citation: J Biol Chem. 2002 Mar 22;277(12):10028-36
references.pmid: 11792697
references.citation: Science. 2010 Oct 15;330(6002):362-6
references.pmid: 20947763
references.citation: J Leukoc Biol. 2006 Dec;80(6):1281-8
references.pmid: 16963624
references.citation: J Clin Invest. 1987 Oct;80(4):1104-13
references.pmid: 3116044
references.citation: Annu Rev Pathol. 2007;2:111-43
references.pmid: 18039095
references.citation: J Cell Biol. 1995 Dec;131(6 Pt 1):1599-608
references.pmid: 8522615
references.citation: J Immunol. 2004 Feb 15;172(4):2578-85
references.pmid: 14764731
references.citation: J Immunol. 2008 May 15;180(10):6439-46
references.pmid: 18453558
references.citation: J Immunol. 2001 Aug 15;167(4):1882-5
references.pmid: 11489966
references.citation: J Leukoc Biol. 2009 Sep;86(3):529-43
references.pmid: 19564575
references.citation: Cell Microbiol. 2006 Nov;8(11):1687-96
references.pmid: 16939535
references.citation: J Clin Invest. 1993 May;91(5):2320-5
references.pmid: 8486793
references.citation: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14298-303
references.pmid: 20660763
references.citation: FASEB J. 2007 Oct;21(12):3162-70
references.pmid: 17496159
references.citation: Cell Microbiol. 2007 Sep;9(9):2299-313
references.pmid: 17697195
references.citation: Am J Physiol Gastrointest Liver Physiol. 2001 Sep;281(3):G705-17
references.pmid: 11518683
references.citation: Biochim Biophys Acta. 1994 Nov 17;1215(1-2):1-8
references.pmid: 7947989
references.citation: Am J Physiol Gastrointest Liver Physiol. 2003 Aug;285(2):G282-90
references.pmid: 12702497
references.citation: J Immunol. 2010 Dec 1;185(11):7026-36
references.pmid: 20974992
references.citation: Nature. 2011 Jun 15;474(7351):298-306
references.pmid: 21677746
references.citation: J Exp Med. 2003 Oct 6;198(7):999-1010
references.pmid: 14530374
references.citation: Science. 1996 Apr 5;272(5258):60-6
references.pmid: 8600538
references.citation: J Cell Biol. 2002 Oct 14;159(1):91-102
references.pmid: 12370241
references.citation: Cell Microbiol. 2011 Dec;13(12):2007-21
references.pmid: 21899702