ArticlePLoS pathogens2016
The Kallikrein-Kinin System: A Novel Mediator of IL-17-Driven Anti-Candida Immunity in the Kidney.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 42 citations in OpenAlex.
- Chimeric PRR T-cell-engager targeting cell surface β-1,3-glucan for invasive candidiasis.PLoS pathogens · 2025Article
- Highly variable antigenic site located at the apex of GII.4 norovirus capsid protein induces cross-reactive blocking antibodies in a variant-specific manner.Journal of virology · 2025Article
- Activation of the Complement/Lectin Pathway, Angiopoietin/Tie-2/VEGF-System, Cytokines and Chemokines in Different Angioedema Subtypes.European journal of immunology · 2025Article
- Potential Pathways and Pathophysiological Implications of Viral Infection-Driven Activation of Kallikrein-Kinin System (KKS).Viruses · 2024Review
- Immune responses to human fungal pathogens and therapeutic prospects.Nature reviews. Immunology · 2023Review
- IL-17: Balancing Protective Immunity and Pathogenesis.Journal of immunology research · 2023Review
- Deep tissue infection by an invasive human fungal pathogen requires lipid-based suppression of the IL-17 response.Cell host & microbe · 2022Article
- Progranulin aggravates lethal Candida albicans sepsis by regulating inflammatory response and antifungal immunity.PLoS pathogens · 2022Article
- Interleukin 17 and Its Involvement in Renal Cell Carcinoma.Journal of clinical medicine · 2022Review
- Systemic Candidiasis in Mice: New Insights From an Old Model.Frontiers in fungal biology · 2022Review
- Local antifungal immunity in the kidney in disseminated candidiasis.Current opinion in microbiology · 2021Review
- Vaccine-Induced Immunological Memory in Invasive Fungal Infections - A Dream so Close yet so Far.Frontiers in immunology · 2021Review
- Review
- Kinins and Their Receptors in Infectious Diseases.Pharmaceuticals (Basel, Switzerland) · 2020Review
- BBritish journal of pharmacology · 2020Article
- Microbiota-driven interleukin-17 production provides immune protection against invasive candidiasis.Critical care (London, England) · 2020Article
- Interleukin-17 in Chronic Inflammatory Neurological Diseases.Frontiers in immunology · 2020Review
- IL-23 supports host defense against systemic Candida albicans infection by ensuring myeloid cell survival.PLoS pathogens · 2019Article
- Article
- The IL-17 Family of Cytokines in Health and Disease.Immunity · 2019Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
The incidence of life-threatening disseminated Candida albicans infections is increasing in hospitalized patients, with fatalities as high as 60%. Death from disseminated candidiasis in a significant percentage of cases is due to fungal invasion of the kidney, leading to renal failure. Treatment of candidiasis is hampered by drug toxicity, the emergence of antifungal drug resistance and lack of vaccines against fungal pathogens. IL-17 is a key mediator of defense against candidiasis. The underlying mechanisms of IL-17-mediated renal immunity have so far been assumed to occur solely through the regulation of antimicrobial mechanisms, particularly activation of neutrophils. Here, we identify an unexpected role for IL-17 in inducing the Kallikrein (Klk)-Kinin System (KKS) in C. albicans-infected kidney, and we show that the KKS provides significant renal protection in candidiasis. Microarray data indicated that Klk1 was upregulated in infected kidney in an IL-17-dependent manner. Overexpression of Klk1 or treatment with bradykinin rescued IL-17RA-/- mice from candidiasis. Therapeutic manipulation of IL-17-KKS pathways restored renal function and prolonged survival by preventing apoptosis of renal cells following C. albicans infection. Furthermore, combining a minimally effective dose of fluconazole with bradykinin markedly improved survival compared to either drug alone. These results indicate that IL-17 not only limits fungal growth in the kidney, but also prevents renal tissue damage and preserves kidney function during disseminated candidiasis through the KKS. Since drugs targeting the KKS are approved clinically, these findings offer potential avenues for the treatment of this fatal nosocomial infection.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.