ArticleInfection and immunity2009
Leptospira interrogans induces apoptosis in macrophages via caspase-8- and caspase-3-dependent pathways.
Article in Infection and immunity, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 90 citations in OpenAlex.
- Leptospiral hemolysins induce proinflammatory cytokines through Toll-like receptor 2-and 4-mediated JNK and NF-κB signaling pathways.PloS one · 2012Trial
- Leptospira interrogans HtrA protease is a potent inducer of multifaceted cellular responses.Antonie van Leeuwenhoek · 2026Article
- Neuroimmune cross-talk inFrontiers in immunology · 2026Review
- MicroRNA biomarkers and host response pathways in severe pulmonary hemorrhagic syndrome due to leptospirosis: A multi-omics study.The Journal of infection · 2025Article
- The Leptospira interrogans proteome's response to zinc highlights the potential involvement of this metal in translational-machinery and virulence.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2024Article
- Single-cell RNA-Seq reveals intracellular microbial diversity within immune cells during SARS-CoV-2 infection and recovery.iScience · 2023Article
- Impaired functions of human monocyte-derived dendritic cells and induction of regulatory T cells by pathogenic Leptospira.PLoS neglected tropical diseases · 2023Article
- Identification of apoptosis-related key genes and the associated regulation mechanism in thoracic aortic aneurysm.BMC cardiovascular disorders · 2023Article
- Effect of Two Different Drug-ResistantFrontiers in veterinary science · 2022Article
- MiR-125b inhibits cardiomyocyte apoptosis by targeting BAK1 in heart failure.Molecular medicine (Cambridge, Mass.) · 2021Article
- Clinical-Pathological Conference Series from the Medical University of Graz : Case No 164: A 46-year-old man with abdominal pain, dyspnea and rapidly progressing multiorgan failure.Wiener klinische Wochenschrift · 2021Article
- Lamin A/C and the Immune System: One Intermediate Filament, Many Faces.International journal of molecular sciences · 2020Review
- Leptospirosis in cats: Current literature review to guide diagnosis and management.Journal of feline medicine and surgery · 2020Review
- Leptospirosis is an invasive infectious and systemic inflammatory disease.Biomedical journal · 2020Review
- Phagocyte Escape ofFrontiers in immunology · 2020Review
- Article
- Gene expression is associated with virulence in murine macrophages infected with Leptospira spp.PloS one · 2019Article
- A novel Fas-binding outer membrane protein and lipopolysaccharide of Leptospira interrogans induce macrophage apoptosis through the Fas/FasL-caspase-8/-3 pathway.Emerging microbes & infections · 2018Article
- Characterization of the microtranscriptome of macrophages infected with virulent, attenuated and saprophyte strains of Leptospira spp.PLoS neglected tropical diseases · 2018Article
- Role of Murine Complement Component C5 in AcuteFrontiers in cellular and infection microbiology · 2018Article
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apoptosis of host cells plays an important role in modulating the pathogenesis of many infectious diseases. It has been reported that Leptospira interrogans, the causal agent of leptospirosis, induces apoptosis in macrophages and hepatocytes. However, the molecular mechanisms responsible for host cell death remained largely unknown. Here we demonstrate that L. interrogans induced apoptosis in a macrophage-like cell line, J774A.1, and primary murine macrophages in a time- and dose-dependent manner. Apoptosis was associated with the activation of cysteine aspartic acid-specific proteases (caspase-3, caspase-6, and caspase-8), the increased expression of Fas-associated death domain (FADD), and the cleavage of the caspase substrates poly(ADP-ribose) polymerase (PARP) and nuclear lamina protein (lamin A and lamin C). Caspase-9 was activated to a lesser extent, whereas no release of cytochrome c from mitochondria was detectable. Inhibition of caspase-8 impaired L. interrogans-induced caspase-3 and -6 activation, as well as PARP and lamin A/C cleavage and apoptosis, suggesting that apoptosis is initiated via caspase-8 activation. Furthermore, caspase-3 was required for the activation of caspase-6 and seemed to be involved in caspase-9 activation through a feedback amplification loop. These data indicate that L. interrogans-induced apoptosis in macrophages is mediated by caspase-3 and -6 activation through a FADD-caspase-8-dependent pathway, independently of mitochondrial cytochrome c-caspase-9-dependent signaling.
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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.