Trial reportPloS one2012
Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-κB signaling pathways.
Trial report in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 2 of them syntheses that pooled it.
What it found
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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
55 citing papers in PubMed, 2 syntheses or guidelines pooled it, 91 citations in OpenAlex.
- Role of Toll-like receptor 2 during infection of Leptospira spp: A systematic review.PloS one · 2024Pooled it
- Cytokine response in human leptospirosis with different clinical outcomes: a systematic review.BMC infectious diseases · 2020Pooled it
- Beyond Acute Infection: A Conceptual Framework Linking Zoonotic Bacterial Pathogens to Pulmonary Fibrosis and Lung Carcinogenesis.Biomedicines · 2026Review
- Multi-omics analysis of human patient samples identifies key immune factors inMicrobiology spectrum · 2026Article
- Navigating a thorny path: oral nanomedicines for the precision management of radiation-induced intestinal injury.Journal of nanobiotechnology · 2026Review
- DMEM and EMEM as alternate growth media for pathogenic Leptospira.PLoS neglected tropical diseases · 2026Article
- Neuroimmune cross-talk inFrontiers in immunology · 2026Review
- Regulation of Necroptosis by Aspergillus fumigatus Exopolysaccharide in Human Macrophages Derived from THP-1 Cells: Involvement of the RIP1-RIP3-MLKL Signaling Axis.Current microbiology · 2025Article
- Leptospirosis.Nature reviews. Disease primers · 2025Review
- DMEM and EMEM are suitable surrogate media to mimic host environment and expand leptospiral pathogenesis studies usingbioRxiv : the preprint server for biology · 2025Article
- A clinical pilot study for the detection of sphingomyelinase in leptospirosis patient's urine at tertiary care hospital.Heliyon · 2023Article
- Weil's Disease-Immunopathogenesis, Multiple Organ Failure, and Potential Role of Gut Microbiota.Biomolecules · 2022Review
- Transcriptome and proteome analysis of innate immune responses to inactivated Leptospira and bivalent Leptospira vaccines in canine 030-D cells.Scientific reports · 2022Article
- Going Micro in Leptospirosis Kidney Disease.Cells · 2022Review
- Screening of Surface-Exposed Lipoproteins ofFrontiers in microbiology · 2022Article
- Extracellular Proteome Analysis Shows the Abundance of Histidine Kinase Sensor Protein, DNA Helicase, Putative Lipoprotein Containing Peptidase M75 Domain and Peptidase C39 Domain Protein inPathogens (Basel, Switzerland) · 2021Article
- GroEL protein of the Leptospira spp. interacts with host proteins and induces cytokines secretion on macrophages.BMC microbiology · 2021Article
- Leptospiral Infection, Pathogenesis and Its Diagnosis-A Review.Pathogens (Basel, Switzerland) · 2021Review
- Comparative Genomic Analysis and a Novel Set of Missense Mutation of theFrontiers in microbiology · 2021Article
- Assessment of Serum Macrophage Migration Inhibitory Factor (MIF) as an Early Diagnostic Marker of Leptospirosis.Frontiers in cellular and infection microbiology · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundInfection with pathogenic Leptospira species causes serious systemic inflammation in patients. Although a few leptospiral proinflammatory molecules have been identified, Leptospira likely encodes other unidentified strong inflammation stimulators. The pathogenic L. interrogans genome encodes numerous putative hemolysin genes. Since hemolysins from other bacteria can cause inflammatory reactions, we hypothesized that leptospiral hemolysins may function as proinflammatory stimulators that contribute to the strong inflammation associated with Leptospira infection. METHODOLOGY/PRINCIPAL
findingsWe first used cytokine protein microarrays for systematic analysis of serum cytokine profiles in leptospirosis patients and leptospire-infected mice. We found that IL-1β, IL-6 and TNF-α were the main proinflammatory cytokines in the sera of both the patients and the mice. We then analyzed eight putative hemolysins in L. interrogans strain Lai. The results showed that five of them, Sph1, Sph2, Sph3, HlpA and TlyA were secreted and had hemolytic activity. More importantly, these five hemolysins induced the strong production of IL-1β, IL-6 and TNF-α in human and mouse macrophages (although a bit lower in the latter). Furthermore, blockade of TLR2 or TLR4 with either antibodies or inhibitors of the NF-κB or JNK signaling pathways significantly reduced the production of hemolysin-induced IL-1β, IL-6 and TNF-α. Macrophages isolated from TLR2-, TLR4-or double TLR2-and 4-deficient mice also confirmed that the leptospiral hemolysins that induce proinflammatory cytokines are both TLR2-and TLR4-dependent. CONCLUSIONS/SIGNIFICANCE: Our findings demonstrate that L. interrogans secretes many hemolysins that function as powerful inducers of proinflammatory cytokines through both TLR2-and TLR4-dependent JNK and NF-κB pathways.
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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.