title: Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury.
abstract: Kidney ischemia-reperfusion injury (IRI) is, in part, mediated by immune and inflammatory factors. Since microbial stimuli are known to alter immune and inflammatory responses, we hypothesized that differences in perinatal microbial status would modify renal injury following IRI. We performed bilateral renal IRI on 6-wk-old germ-free and control mice and studied the effects on kidney lymphocyte trafficking, cytokines, function, and structure. Compared with control mice, normal kidneys of germ-free mice exhibited more NKT cells and lower IL-4 levels. Postischemia, more CD8 T cells trafficked into postischemic kidneys of germ-free mice compared with control mice. Renal structural injury and functional decline following IRI were more severe in germ-free mice compared with control mice. When germ-free mice were conventionalized with the addition of bacteria to their diet, the extent of renal injury after IRI became equivalent to age-matched control mice, with similar numbers and phenotypes of T cells and NKT cells, as well as cytokine expression in both normal kidneys and postischemic kidneys of conventionalized germ-free mice and age-matched control mice. Thus microbial stimuli influence the phenotype of renal lymphocytes and the expression of cytokines of normal kidneys and also modulate the outcome of IRI.
authors.affiliation: Nephrology Division, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Hye Ryoun
authors.initials: HR
authors.lastname: Jang
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Gandolfo
authors.forename: Gang Jee
authors.initials: GJ
authors.lastname: Ko
authors.forename: Shailesh
authors.initials: S
authors.lastname: Satpute
authors.forename: Lorraine
authors.initials: L
authors.lastname: Racusen
authors.forename: Hamid
authors.initials: H
authors.lastname: Rabb
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000382:microbiology / Q000502:physiology; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D005856:Germ-Free Life; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D007422:Intestines / Q000382:microbiology; D007674:Kidney Diseases / Q000382:microbiology* / Q000473:pathology*; D007677:Kidney Function Tests; D007679:Kidney Medulla / Q000382:microbiology / Q000473:pathology; D007684:Kidney Tubules / Q000382:microbiology / Q000473:pathology; D018655:Lymphocyte Count; D008297:Male; D051379:Mice; D009000:Monocytes / Q000502:physiology; D009393:Nephritis / Q000382:microbiology* / Q000473:pathology*; D010641:Phenotype; D015427:Reperfusion Injury / Q000382:microbiology* / Q000473:pathology*; D013601:T-Lymphocytes / Q000382:microbiology / Q000502:physiology
chemical_list: D016207:Cytokines; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma
references.citation: Diabetes. 1990 May;39(5):583-9
references.pmid: 2139617
references.citation: BMJ. 2000 Jul 8;321(7253):88-92
references.pmid: 10884260
references.citation: Kidney Int. 2001 Oct;60(4):1415-27
references.pmid: 11576355
references.citation: Pediatr Allergy Immunol. 1999 May;10(2):107-11
references.pmid: 10478612
references.citation: Respir Res. 2001;2(3):129-32
references.pmid: 11686875
references.citation: Neurology. 1988 Mar;38(3):384-8
references.pmid: 3347341
references.citation: Immunobiology. 2007;212(6):441-52
references.pmid: 17544829
references.citation: J Immunol. 2007 Feb 1;178(3):1791-9
references.pmid: 17237429
references.citation: Lancet. 2000 Mar 11;355(9207):873-6
references.pmid: 10752702
references.citation: Am J Physiol. 1996 Aug;271(2 Pt 2):F408-13
references.pmid: 8770173
references.citation: Science. 2002 Apr 19;296(5567):490-4
references.pmid: 11964470
references.citation: Am J Physiol Renal Physiol. 2007 Sep;293(3):F713-22
references.pmid: 17596528
references.citation: Transplantation. 2002 Sep 27;74(6):759-63
references.pmid: 12364852
references.citation: Crit Care Med. 2000 Jul;28(7):2507-14
references.pmid: 10921586
references.citation: Kidney Int. 2004 Aug;66(2):491-6
references.pmid: 15253695
references.citation: Science. 1972 Feb 18;175(4023):784-6
references.pmid: 4536694
references.citation: J Clin Invest. 1997 Jun 1;99(11):2682-90
references.pmid: 9169498
references.citation: Eur J Immunol. 2004 Apr;34(4):981-9
references.pmid: 15048708
references.citation: Nat Med. 2002 Jun;8(6):625-9
references.pmid: 12042815
references.citation: Immunology. 2004 Aug;112(4):624-30
references.pmid: 15270734
references.citation: Nature. 2008 Oct 23;455(7216):1109-13
references.pmid: 18806780
references.citation: J Gerontol A Biol Sci Med Sci. 2005 Jul;60(7):830-9
references.pmid: 16079204
references.citation: Am J Physiol Renal Physiol. 2003 Aug;285(2):F319-25
references.pmid: 12709397
references.citation: J Immunol. 2008 Aug 15;181(4):2741-52
references.pmid: 18684965
references.citation: J Immunol. 2007 Dec 15;179(12):8533-43
references.pmid: 18056401
references.citation: Am J Physiol Renal Physiol. 2000 Sep;279(3):F525-31
references.pmid: 10966932
references.citation: BMJ. 1989 Nov 18;299(6710):1259-60
references.pmid: 2513902
references.citation: J Clin Invest. 2001 Nov;108(9):1283-90
references.pmid: 11696572
references.citation: Immunol Cell Biol. 1997 Oct;75(5):467-71
references.pmid: 9429894
references.citation: Curr Opin Immunol. 1994 Dec;6(6):838-46
references.pmid: 7710707
references.citation: J Am Soc Nephrol. 1998 Feb;9(2):231-42
references.pmid: 9527399
references.citation: Clin Immunol. 2009 Jan;130(1):41-50
references.pmid: 18922742
references.citation: J Immunol. 2004 Mar 15;172(6):3842-9
references.pmid: 15004191
references.citation: J Autoimmun. 1992 Dec;5(6):675-90
references.pmid: 1489483
references.citation: Nat Rev Immunol. 2001 Oct;1(1):69-75
references.pmid: 11905816
references.citation: J Clin Invest. 1996 Feb 15;97(4):1056-63
references.pmid: 8613529
references.citation: N Engl J Med. 1996 May 30;334(22):1448-60
references.pmid: 8618585
references.citation: N Engl J Med. 2002 Sep 19;347(12):911-20
references.pmid: 12239261
references.citation: Nature. 1970 Apr 18;226(5242):266-7
references.pmid: 5437516
references.citation: J Immunol. 2008 Sep 1;181(5):3243-51
references.pmid: 18713995
references.citation: J Immunol. 2004 Sep 15;173(6):4137-46
references.pmid: 15356164
references.citation: J Leukoc Biol. 2008 Dec;84(6):1400-9
references.pmid: 18765477
references.citation: J Immunol. 2007 May 1;178(9):5899-911
references.pmid: 17442974
references.citation: J Immunol. 2001 Jan 15;166(2):1352-9
references.pmid: 11145720
references.citation: J Immunol. 2006 Sep 1;177(5):3380-7
references.pmid: 16920979
references.citation: Nephron. 2002 Feb;90(2):133-8
references.pmid: 11818695
references.citation: J Immunol. 2003 Mar 15;170(6):3289-95
references.pmid: 12626588
references.citation: Kidney Int. 2008 Feb;73(3):318-26
references.pmid: 18004294
references.citation: Lancet. 2004 Feb 21;363(9409):608-15
references.pmid: 14987885
references.citation: Hepatology. 2003 Feb;37(2):296-303
references.pmid: 12540779