Buelli Simona, Zoja Carlamaria, Remuzzi Giuseppe, Morigi Marina
Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Centro Anna Maria Astori, Science and Technology Park Kilometro Rosso, 24126 Bergamo, Italy.
L. Sacco Department of Biomedical and Clinical Sciences, University of Milan, 20157 Milan, Italy.
Microorganisms. 2019 Jan 10;7(1):15. doi: 10.3390/microorganisms7010015.
Shiga toxin (Stx)-producing (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.
产志贺毒素（Stx）的大肠杆菌（STEC）感染已成为全球公共卫生的一大威胁，因为它们可引发严重疾病，如出血性结肠炎和腹泻后溶血尿毒综合征（HUS），其特征为微血管病性溶血性贫血、血小板减少和急性肾衰竭。肾小球内皮细胞是Stx的主要靶标，Stx与其特异性受体球三糖神经酰胺结合后，会上调参与白细胞募集和黏附以及内皮损伤部位血栓形成的促炎蛋白。在本综述中，我们讨论补体激活在促进肾小球微血管功能障碍中的作用，并提供来自实验模型和STEC-HUS患者的证据。在肾小球内，Stx诱导补体激活的一个重要靶标是足细胞，足细胞是一种与内皮细胞紧密接触并参与维持滤过屏障的细胞类型。最近，足细胞损伤和丢失已被指出是STEC-HUS患者长期肾脏后遗症的潜在危险因素。针对补体系统的治疗方法可能是STEC-HUS患者的有用选择，我们也将对此进行讨论。
