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Microorganisms 2019, 7(1), 15; https://doi.org/10.3390/microorganisms7010015

Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome

1
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, Italy
2
L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy
*
Author to whom correspondence should be addressed.
Received: 19 November 2018 / Revised: 21 December 2018 / Accepted: 7 January 2019 / Published: 10 January 2019
(This article belongs to the Special Issue Pathogenesis of Enterohaemorrhagic Escherichia coli)
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Abstract

Shiga toxin (Stx)-producing Escherichia coli (STEC) infections have become a threat to public health globally because of the severe illnesses that they can trigger, such as hemorrhagic colitis and the post-diarrheal hemolytic uremic syndrome (HUS), characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney failure. Glomerular endothelial cells are primary targets of Stx which, after binding to its specific receptor globotriaosylceramide, upregulates proinflammatory proteins involved both in the recruitment and adhesion of leukocytes and thrombus formation at the site of endothelial injury. In this review, we discuss the role of complement activation in promoting glomerular microvascular dysfunction, providing evidence from experimental models and patients with STEC-HUS. Within the glomerulus, an important target for Stx-induced complement activation is the podocyte, a cell type that is in close contact with endothelial cells and participates in maintaining the filtration barrier. Recently, podocyte injury and loss have been indicated as potential risk factors for long-term renal sequelae in patients with STEC-HUS. Therapeutic approaches targeting the complement system, that may be useful options for patients with STEC-HUS, will also be discussed. View Full-Text
Keywords: Shiga toxin; hemolytic uremic syndrome; endothelial damage; microvascular thrombosis; podocytes; complement alternative pathway; long-term renal sequelae Shiga toxin; hemolytic uremic syndrome; endothelial damage; microvascular thrombosis; podocytes; complement alternative pathway; long-term renal sequelae
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).
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Buelli, S.; Zoja, C.; Remuzzi, G.; Morigi, M. Complement Activation Contributes to the Pathophysiology of Shiga Toxin-Associated Hemolytic Uremic Syndrome. Microorganisms 2019, 7, 15.

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