Early exposure to germs modifies kidney damage and inflammation after experimental ischemia-reperfusion injury

Am J Physiol Renal Physiol. 2009 Nov;297(5):F1457-65. doi: 10.1152/ajprenal.90769.2008. Epub 2009 Aug 12.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / microbiology
  • CD8-Positive T-Lymphocytes / physiology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Germ-Free Life
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-4 / biosynthesis
  • Intestines / microbiology
  • Kidney Diseases / microbiology*
  • Kidney Diseases / pathology*
  • Kidney Function Tests
  • Kidney Medulla / microbiology
  • Kidney Medulla / pathology
  • Kidney Tubules / microbiology
  • Kidney Tubules / pathology
  • Lymphocyte Count
  • Male
  • Mice
  • Monocytes / physiology
  • Nephritis / microbiology*
  • Nephritis / pathology*
  • Phenotype
  • Reperfusion Injury / microbiology*
  • Reperfusion Injury / pathology*
  • T-Lymphocytes / microbiology
  • T-Lymphocytes / physiology


  • Cytokines
  • Interleukin-10
  • Interleukin-4
  • Interferon-gamma