ArticlePLoS pathogens2016
Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.
Article in PLoS pathogens, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it, 39 citations in OpenAlex.
- A consensus immune dysregulation framework for sepsis and critical illnesses.Nature medicine · 2025Guideline
- Early diagnosis and treatment of leptospirosis: Optimizing clinical outcomes.The Journal of infection · 2026Review
- Article
- TLR4 competence and mouse models of sublethal leptospirosis.PLoS neglected tropical diseases · 2025Article
- Myocarditis and neutrophil-mediated vascular leakage but not cytokine storm associated with fatal murine leptospirosis.EBioMedicine · 2025Article
- MicroRNA biomarkers and host response pathways in severe pulmonary hemorrhagic syndrome due to leptospirosis: A multi-omics study.The Journal of infection · 2025Article
- Quantitative and Longitudinal Assessment of Systemic Innate Immunity in Health and Disease Using a 2D Gene Model.Biomedicines · 2024Article
- A robust host-response-based signature distinguishes bacterial and viral infections across diverse global populations.Cell reports. Medicine · 2022Article
- Role of Diagnostics in Epidemiology, Management, Surveillance, and Control of Leptospirosis.Pathogens (Basel, Switzerland) · 2022Review
- Pathogenesis insights from an ancient and ubiquitous spirochete.PLoS pathogens · 2021Review
- The role of leptospiremia and specific immune response in severe leptospirosis.Scientific reports · 2021Article
- Leptospiral LPS escapes mouse TLR4 internalization and TRIF‑associated antimicrobial responses through O antigen and associated lipoproteins.PLoS pathogens · 2020Article
- Phagocyte Escape ofFrontiers in immunology · 2020Review
- Escape of TLR5 Recognition byFrontiers in immunology · 2020Article
- Increased inflammation with crudeEmerging microbes & infections · 2020Article
- Elevated Activation of Neutrophil Toll-Like Receptors in Patients with Acute Severe Leptospirosis: An Observational Study.The American journal of tropical medicine and hygiene · 2019Observational
- Cathelicidin-OA1, a novel antioxidant peptide identified from an amphibian, accelerates skin wound healing.Scientific reports · 2018Article
- Correction: Cathelicidin Insufficiency in Patients with Fatal Leptospirosis.PLoS pathogens · 2017Article
- Virulence of the zoonotic agent of leptospirosis: still terra incognita?Nature reviews. Microbiology · 2017Review
- Automation of sample preparation for mass cytometry barcoding in support of clinical research: protocol optimization.Analytical and bioanalytical chemistry · 2017Article
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 5 institutions in 2 countries.
Funding
Abstract
Leptospirosis causes significant morbidity and mortality worldwide; however, the role of the host immune response in disease progression and high case fatality (>10-50%) is poorly understood. We conducted a multi-parameter investigation of patients with acute leptospirosis to identify mechanisms associated with case fatality. Whole blood transcriptional profiling of 16 hospitalized Brazilian patients with acute leptospirosis (13 survivors, 3 deceased) revealed fatal cases had lower expression of the antimicrobial peptide, cathelicidin, and chemokines, but more abundant pro-inflammatory cytokine receptors. In contrast, survivors generated strong adaptive immune signatures, including transcripts relevant to antigen presentation and immunoglobulin production. In an independent cohort (23 survivors, 22 deceased), fatal cases had higher bacterial loads (P = 0.0004) and lower anti-Leptospira antibody titers (P = 0.02) at the time of hospitalization, independent of the duration of illness. Low serum cathelicidin and RANTES levels during acute illness were independent risk factors for higher bacterial loads (P = 0.005) and death (P = 0.04), respectively. To investigate the mechanism of cathelicidin in patients surviving acute disease, we administered LL-37, the active peptide of cathelicidin, in a hamster model of lethal leptospirosis and found it significantly decreased bacterial loads and increased survival. Our findings indicate that the host immune response plays a central role in severe leptospirosis disease progression. While drawn from a limited study size, significant conclusions include that poor clinical outcomes are associated with high systemic bacterial loads, and a decreased antibody response. Furthermore, our data identified a key role for the antimicrobial peptide, cathelicidin, in mounting an effective bactericidal response against the pathogen, which represents a valuable new therapeutic approach for leptospirosis.
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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.