Cytokine Production Is Altered in Monocytes from Children with Hemolytic Uremic Syndrome

Fernández, Gabriela; Ramos, María Victoria Carballo Calero; Landoni, Verónica Inés; Bentancor, Leticia V.; Fernández-Brando, Romina Jimena; Exeni, Ramón; Laso, María del Carmen; Exeni, Andrea; Grimoldi, Irene; Isturiz, Martı́n A.; Palermo, Marina S.

doi:10.1007/s10875-011-9646-z

Cited by 8 publications

(6 citation statements)

References 48 publications

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“…Stx-HUS patients also show a correlation between monocytosis and HUS severity [89], together with changes in the expression of chemokine receptors on these cells [89][90][91]. In particular, a selective depletion of circulating mononuclear leukocytes expressing the receptor for fractalkine/CX 3 CL1 (CX 3 CR1) was observed, that correlates with the severity of renal failure [92].…”

Section: Monocytes/macrophagesmentioning

confidence: 97%

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

Exeni¹,

Fernández-Brando

Santiago³

et al. 2018

Pediatr Nephrol

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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.

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Section: Monocytes/macrophagesmentioning

confidence: 97%

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

Exeni¹,

Fernández-Brando

Santiago³

et al. 2018

Pediatr Nephrol

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“…CD16 is a marker of activation in monocytes, and corresponds to increases in proinflammatory cytokine secretion, which are seen in early CHIKV infection 30,31 . A considerable increase in the number of CD14+CD16+ monocytes had been described for a variety of systemic, infectious agents in humans, including hemolytic uremic syndrome 32 , bacterial sepsis 33 , HIV 34 , and experimental SIV infections in nonhuman primates 35 .…”

Section: Discussionmentioning

confidence: 99%

Phenotypic and Kinetic Changes of Myeloid Lineage Cells in Innate Response to Chikungunya Infection in Cynomolgus Macaques

Sugimoto

Kuroda

et al. 2021

Preprint

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Chikungunya is an emerging threat, spreading across multiple continents. The immune response to infection can lead to protection and convalescence, or result in long term sequelae such as arthritis. Early innate immune events during acute infection have been characterized for some cell types, but more must be elucidated with respect to cellular responses of monocytes and other myeloid lineage cells. In addition to their roles in protection and inflammation resolution, monocytes and macrophages are sites for viral replication and reservoirs for the virus. They are also found in joints post-infection, possibly playing a role in long term CHIKV-induced pathology. We examined kinetic and phenotypic changes in myeloid lineage cells, including monocytes, in cynomolgus macaques early after infection with CHIKV. We found increased turnover of monocytes and mDCs early during infection, with an accompanying decreases in both cell types, as well as a simultaneous increase in pDC number. An increase in CD16 and CD14 was seen along with a decrease in monocyte HLA-DR expression within 3 days of infection, potentially indicating monocyte deactivation. A transient decrease in T cells, B cells and NK cells correlates with lymphocytopenia observed during human infections with CHIKV. CD4+ T cell turnover decreased in blood, indicating relocation of cells to effector sites. This data indicates CHIKV influences turnover rates and kinetics of myeloid lineage cells early during infection, and may prove useful in development of therapeutics and evaluation of infection-induced pathogenesis.

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“…Patients with STEC–HUS have higher plasma levels of TNF-α, IL-6, and lower levels of IL-10 compared to normal controls, a process driven in part by increased expression of Toll-like receptor on circulating PMN ( 37 , 38 ). Isolated monocytes from children with STEC–HUS that are incubated with Stx1 produce IL-1β, IL-6, IL-8, and TNF-α ( 39 ).…”

Section: Pathophysiologymentioning

confidence: 99%

“…Similarly, monocyte production of TNF-α and IL-10 increases in parallel with the intensity of disease in children with STEC–HUS. Patients with moderate-to-severe disease had the greatest number of TNF-α producing monocytes ( 38 ). Patients who progressed to severe renal dysfunction had a 10-fold increase in IL-6 compared to those who maintained diuresis ( 41 ).…”

Section: Pathophysiologymentioning

confidence: 99%

Hemolytic Uremic Syndrome: Toxins, Vessels, and Inflammation

Cheung

Trachtman

2014

Front. Med.

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Hemolytic uremic syndrome (HUS) is characterized by thrombotic microangiopathy of the glomerular microcirculation and other vascular beds. Its defining clinical phenotype is acute kidney injury (AKI), microangiopathic anemia, and thrombocytopenia. There are many etiologies of HUS including infection by Shiga toxin-producing bacterial strains, medications, viral infections, malignancy, and mutations of genes coding for proteins involved in the alternative pathway of complement. In the aggregate, although HUS is a rare disease, it is one of the most common causes of AKI in previously healthy children and accounts for a sizable number of pediatric and adult patients who progress to end stage kidney disease. There has been great progress over the past 20 years in understanding the pathophysiology of HUS and its related disorders. There has been intense focus on vascular injury in HUS as the major mechanism of disease and target for effective therapies for this acute illness. In all forms of HUS, there is evidence of both systemic and intra-glomerular inflammation and perturbations in the immune system. Renewed investigation into these aspects of HUS may prove helpful in developing new interventions that can attenuate glomerular and tubular injury and improve clinical outcomes in patients with HUS.

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Cytokine Production Is Altered in Monocytes from Children with Hemolytic Uremic Syndrome

Abstract: These results indicate that Mo from severe cases of HUS, similar to IC but different to mild HUS cases, present functional changes in Mo subpopulations and abnormal responses to LPS.

Cited by 8 publications

References 48 publications

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

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

Phenotypic and Kinetic Changes of Myeloid Lineage Cells in Innate Response to Chikungunya Infection in Cynomolgus Macaques

Hemolytic Uremic Syndrome: Toxins, Vessels, and Inflammation

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