title: Distinct renal pathology and a chemotactic phenotype after enterohemorrhagic Escherichia coli shiga toxins in non-human primate models of hemolytic uremic syndrome.
abstract: Enterohemorrhagic Escherichia coli cause approximately 1.5 million infections globally with 176,000 cases occurring in the United States annually from ingesting contaminated food, most frequently E. coli O157:H7 in ground beef or fresh produce. In severe cases, the painful prodromal hemorrhagic colitis is complicated by potentially lethal hemolytic uremic syndrome (HUS), particularly in children. Bacterial Shiga-like toxins (Stx1, Stx2) are primarily responsible for HUS and the kidney and neurologic damage that ensue. Small animal models are hampered by the inability to reproduce HUS with thrombotic microangiopathy, hemolytic anemia, and acute kidney injury. Earlier, we showed that nonhuman primates (Papio) recapitulated clinical HUS after Stx challenge and that novel therapeutic intervention rescued the animals. Here, we present detailed light and electron microscopic pathology examination of the kidneys from these Stx studies. Stx1 challenge resulted in more severe glomerular endothelial injury, whereas the glomerular injury after Stx2 also included prominent mesangiolysis and an eosinophilic inflammatory infiltration. Both toxins induced glomerular platelet-rich thrombi, interstitial hemorrhage, and tubular injury. Analysis of kidney and other organs for inflammation biomarkers showed a striking chemotactic profile, with extremely high mRNA levels for IL-8, monocyte chemoattractant protein 1, and macrophage inflammatory protein 1α and elevated urine chemokines at 48 hours after challenge. These observations give unique insight into the pathologic consequences of each toxin in a near human setting and present potential pathways for therapeutic intervention.
authors: Department of Pathology and Laboratory Medicine, Boston University School of Medicine, Boston, Massachusetts 02118, USA.
authors: Deborah J
authors: DJ
authors: Stearns-Kurosawa
authors: Sun-Young
authors: SY
authors: Oh
authors: Rama P
authors: RP
authors: Cherla
authors: Moo-Seung
authors: MS
authors: Lee
authors: Vernon L
authors: VL
authors: Tesh
authors: James
authors: J
authors: Papin
authors: Joel
authors: J
authors: Henderson
authors: Shinichiro
authors: S
authors: Kurosawa
mesh_terms: D000818:Animals; D018925:Chemokines / Q000235:genetics / Q000652:urine; D002633:Chemotaxis; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D054324:Enterohemorrhagic Escherichia coli / Q000502:physiology*; D004804:Eosinophils / Q000473:pathology; D005786:Gene Expression Regulation; D006463:Hemolytic-Uremic Syndrome / Q000235:genetics / Q000382:microbiology* / Q000473:pathology* / Q000652:urine; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007668:Kidney / Q000378:metabolism / Q000382:microbiology / Q000473:pathology* / Q000648:ultrastructure; D050527:Mesangial Cells / Q000378:metabolism / Q000382:microbiology / Q000473:pathology / Q000648:ultrastructure; D010215:Papio / Q000382:microbiology*; D010641:Phenotype; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D022622:Shiga Toxin 1 / Q000378:metabolism; D022641:Shiga Toxin 2 / Q000378:metabolism; D022603:Shiga Toxins / Q000378:metabolism*
chemical_list: D018925:Chemokines; D012333:RNA, Messenger; D022622:Shiga Toxin 1; D022641:Shiga Toxin 2; D022603:Shiga Toxins
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