Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome

Lill, Julia K.; Thiebes, Stephanie; Pohl, Judith-Mira; Bottek, Jenny; Subramaniam, Nirojah; Christ, Robin; Soun, Camille; Gueler, Faikah; Zwanziger, Denise; Hoffmann, Franziska; Eggeling, Ferdinand von; Bracht, Thilo; Sitek, Barbara; Hickey, Michael J.; Hofnagel, Oliver; Engel, Daniel R.

doi:10.1016/j.kint.2021.03.039

Cited by 6 publications

(3 citation statements)

References 64 publications

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“…Elevated biomarkers: lipocalin 2, IL-8, IL-10, and neopterin are observed in HUS; however, mechanisms of activation are not fully understood [114,122,123]. E. coli O157:H7 infection activates tissue-resident macrophages that mediate CXCR2-dependent neutrophil recruitment and kidney injury [124]. A recent study by Lee et al shows that Stx-containing exosomes derived from peripheral blood mononuclear cells and macrophages have significantly increased proinflammatory effects on proximal tubular cells [28].…”

Section: Inflammationmentioning

confidence: 99%

Escherichia coli 0157:H7 virulence factors and the ruminant reservoir

Kolodziejek

Minnich

Hovde

2022

Current Opinion in Infectious Diseases

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Purpose of reviewThis review updates recent findings about Escherichia coli O157:H7 virulence factors and its bovine reservoir. This Shiga toxin (Stx)-producing E. coli belongs to the Enterohemorrhagic E. coli (EHEC) pathotype causing hemorrhagic colitis. Its low infectious dose makes it an efficient, severe, foodborne pathogen. Although EHEC remains in the intestine, Stx can translocate systemically and is cytotoxic to microvascular endothelial cells, especially in the kidney and brain. Disease can progress to life-threatening hemolytic uremic syndrome (HUS) with hemolytic anemia, acute kidney failure, and thrombocytopenia. Young children, the immunocompromised, and the elderly are at the highest risk for HUS. Healthy ruminants are the major reservoir of EHEC and cattle are the primary source of human exposure.

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Section: Inflammationmentioning

confidence: 99%

Escherichia coli 0157:H7 virulence factors and the ruminant reservoir

Kolodziejek

Minnich

Hovde

2022

Current Opinion in Infectious Diseases

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“…Multiple cell types have been implicated, including damaged proximal tubules and vascular cells in addition to leukocytes (47). KRMs are of particular interest given their capacity for inflammation and fibrosis and continued presence in the tissue beyond an acute injury (48)(49)(50)(51)(52). Future studies should consider the effect of the altered KRM subpopulations on long-term kidney function both from native kidneys and the following transplant.…”

Section: Discussionmentioning

confidence: 99%

Resident macrophage subpopulations occupy distinct microenvironments in the kidney

Cheung¹,

Erman²,

Moore³

et al. 2022

JCI Insight

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The kidney contains a population of resident macrophages from birth that expands as it grows and forms a contiguous network throughout the tissue. Kidney-resident macrophages (KRMs) are important in homeostasis and the response to acute kidney injury. While the kidney contains many microenvironments, it is unknown whether KRMs are a heterogeneous population differentiated by function and location. We combined single-cell RNA-Seq (scRNA-Seq), spatial transcriptomics, flow cytometry, and immunofluorescence imaging to localize, characterize, and validate KRM populations during quiescence and following 19 minutes of bilateral ischemic kidney injury. scRNA-Seq and spatial transcriptomics revealed 7 distinct KRM subpopulations, which are organized into zones corresponding to regions of the nephron. Each subpopulation was identifiable by a unique transcriptomic signature, suggesting distinct functions. Specific protein markers were identified for 2 clusters, allowing analysis by flow cytometry or immunofluorescence imaging. Following injury, the original localization of each subpopulation was lost, either from changing locations or transcriptomic signatures. The original spatial distribution of KRMs was not fully restored for at least 28 days after injury. The change in KRM localization confirmed a long-hypothesized dysregulation of the local immune system following acute injury and may explain the increased risk for chronic kidney disease.

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“…Although the mechanisms underlying neutrophil recruitment in the kidney remain quite understudied, it is now known that it can occur in all three distinct capillary networks found in this organ and that various proteins, e.g., P-selectin, E-selectin, intercellular adhesion molecule 1 (ICAM-1), β2-integrins and P-selectin glycoprotein ligand-1 (PSGL-1), can be of importance depending on the exact location [40]. Furthermore, upon infection with Shiga-toxin-producing enterohemorrhagic E. coli, neutrophil recruitment was dependent on TNF-α, CXCL1 and CXCL2 produced by tissue-resident macrophages and was directly associated with kidney injury and poor disease outcomes [50]. This is not the first study highlighting the contradictory role of neutrophils, as their presence in kidneys has been extensively correlated with poor prognosis for patients suffering from acute kidney injury, renal cancer, diabetic kidney disease and renal failure [51][52][53].…”

Section: Neutrophils In the Kidneysmentioning

confidence: 99%

The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease

Tsioumpekou,

Krijgsman,

Leusen

et al. 2023

Cells

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Neutrophils are crucial innate immune cells and comprise 50–70% of the white blood cell population under homeostatic conditions. Upon infection and in cancer, blood neutrophil numbers significantly increase because of the secretion of various chemo- and cytokines by, e.g., leukocytes, pericytes, fibroblasts and endothelial cells present in the inflamed tissue or in the tumor microenvironment (TME). The function of neutrophils in cancer has recently gained considerable attention, as they can exert both pro- and anti-tumorigenic functions, dependent on the cytokine milieu present in the TME. Here, we review the effect of cytokines on neutrophil development, tissue homing, function and plasticity in cancer and autoimmune diseases as well as under physiological conditions in the bone marrow, bloodstream and various organs like the spleen, kidney, liver, lung and lymph nodes. In addition, we address several promising therapeutic options, such as cytokine therapy, immunocytokines and immunotherapy, which aim to exploit the anti-tumorigenic potential of neutrophils in cancer treatment or block excessive neutrophil-mediated inflammation in autoimmune diseases.

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Tissue-resident macrophages mediate neutrophil recruitment and kidney injury in shiga toxin-induced hemolytic uremic syndrome

Cited by 6 publications

References 64 publications

Escherichia coli 0157:H7 virulence factors and the ruminant reservoir

Escherichia coli 0157:H7 virulence factors and the ruminant reservoir

Resident macrophage subpopulations occupy distinct microenvironments in the kidney

The Role of Cytokines in Neutrophil Development, Tissue Homing, Function and Plasticity in Health and Disease

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