Pathogenic role of inflammatory response during Shiga toxin-associated hemolytic uremic syndrome (HUS)

Abstract

Hemolytic uremic syndrome (HUS) is defined as a triad of noninmune microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. The most frequent presentation is secondary to Shiga toxin (Stx)-producing Escherichia coli (STEC) infections, which is termed postdiarrheal, epidemiologic or Stx-HUS, considering that Stx is the necessary etiological factor. After ingestion, STEC colonize the intestine and produce Stx, which translocates across the intestinal epithelium. Once Stx enters the bloodstream, it interacts with renal endothelial and epithelial cells, and leukocytes. This review summarizes the current evidence about the involvement of inflammatory components as central pathogenic factors that could determine outcome of STEC infections. Intestinal inflammation may favor epithelial leakage and subsequent passage of Stx to the systemic circulation. Vascular damage triggered by Stx promotes not only release of thrombin and increased fibrin concentration but also production of cytokines and chemokines by endothelial cells. Recent evidence from animal models and patients strongly indicate that several immune cells types may participate in HUS physiopathology: neutrophils, through release of proteases and reactive oxygen species (ROS); monocytes/macrophages through secretion of cytokines and chemokines. In addition, high levels of Bb factor and soluble C5b-9 (sC5b-9) in plasma as well as complement factors adhered to platelet-leukocyte complexes, microparticles and microvesicles, suggest activation of the alternative pathway of complement. Thus, acute immune response secondary to STEC infection, the Stx stimulatory effect on different immune cells, and inflammatory stimulus secondary to endothelial damage all together converge to define a strong inflammatory status that worsens Stx toxicity and disease.

Identification of pathogenic bacteria on the salted fish Lutjanus vivanus in Sorong City of West Papua

“…It represented the sample TC, sample PN, and sample PO. β hemolysis is defined as the lysis of all red blood cells, which is characterized by forming a clear zone approaching the color and transparency of basic media (Buhnik-Rosenblau et al, 2013;Exeni et al, 2018 ). Amplification of Genomic DNA in sample KS and LG by PCR method using primers 63f and 1387r produced DNA fragments measuring around 1300 pb (Figure 2).…”

Cerebral sinovenous thrombosis in pediatric hemolytic uremic syndrome

“…At its core, HUS is a disorder of microangiopathy precipitated by endothelial injury leading to inflammation and formation of thrombi. While this provides a theoretical basis for development of thrombotic complications in large vessels, it does not explain why thrombotic complications in HUS generally tend to occur in the microvasculature rather than large vessels 1,7 …”

“…HUS is associated with elevations in prothrombotic coagulation factors, including factor VIII, which could contribute to an overall prothrombotic predisposition. For example, Shiga toxin promotes the release of thrombin and increases fibrin concentration 7 . Shiga toxin has also been found to promote ultra‐large von Willebrand factor multimers, which can contribute to a prothrombotic state, 8 and HUS is also associated with elevations of the prothrombotic factor plasminogen activator inhibitor‐1 9 .…”

Prevalence of Shiga toxin-producing and Enteropathogenic Escherichia coli Isolated from Chicken Meat in the west of Iran

“…In addition to Shiga toxins, an external membrane protein called intimin is responsible for the attachment of bacteria to the intestinal epithelial cells, causes a certain damage (attaching-effacing lesions (A/E)), and is encoded by the eae gene [3,4]. Also, enterohemolysin, encoded by the hly gene, is an effective factor in the pathogenicity of STEC [5].…”