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Am J Physiol Renal Physiol 297: F1457-F1465, 2009. First published August 12, 2009; doi:10.1152/ajprenal.90769.2008
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Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury

Hye Ryoun Jang,1 Maria Teresa Gandolfo,2 Gang Jee Ko,1 Shailesh Satpute,1 Lorraine Racusen,2 and Hamid Rabb1

1Nephrology Division, Department of Medicine, and ; 2Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland

Submitted December 28, 2008 ; accepted in final form August 7, 2009

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.

germ-free status; immune modulation


Address for reprint requests and other correspondence: H. Rabb, Div. of Nephrology, Johns Hopkins University School of Medicine, Ross Bldg., Rm. 965, 720 Rutland Ave., Baltimore, MD 21205 (e-mail: hrabb1{at}jhmi.edu).






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