ArticlePLoS pathogens2013
Adhesion of Neisseria meningitidis to dermal vessels leads to local vascular damage and purpura in a humanized mouse model.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed, 103 citations in OpenAlex.
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- Diclofenac sensitizes multi-drug resistant Acinetobacter baumannii to colistin.PLoS pathogens · 2024Article
- Cryo-EM structures of type IV pili complexed with nanobodies reveal immune escape mechanisms.Nature communications · 2024Article
- Vertebrate and Invertebrate Animal and New In Vitro Models for StudyingPathogens (Basel, Switzerland) · 2023Review
- Implantation of engineered human microvasculature to study human infectious diseases in mouse models.iScience · 2023Article
- Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis.Clinical and translational medicine · 2023Review
- Landmark Discoveries and Recent Advances in Type IV Pilus Research.Microbiology and molecular biology reviews : MMBR · 2022Review
- Understanding purpura fulminans in adult patients.Intensive care medicine · 2022Article
- Colonization of dermal arterioles by Neisseria meningitidis provides a safe haven from neutrophils.Nature communications · 2021Article
- Humanized Mice as a Tool to Study Sepsis-More Than Meets the Eye.International journal of molecular sciences · 2021Review
- Type IV pilus retraction enables sustained bacteremia and plays a key role in the outcome of meningococcal sepsis in a humanized mouse model.PLoS pathogens · 2021Article
- Interactions and Signal Transduction Pathways Involved during Central Nervous System Entry byInternational journal of molecular sciences · 2020Review
- Evidence for Multi-Organ Infection During Experimental Meningococcal Sepsis due to ST-11 Isolates in Human Transferrin-Transgenic Mice.Microorganisms · 2020Article
- Development of humanized mouse and rat models with full-thickness human skin and autologous immune cells.Scientific reports · 2020Article
- Developing a xenograft model of human vasculature in the mouse ear pinna.Scientific reports · 2020Article
- Extensive Changes in Transcriptomic "Fingerprints" and Immunological Cells in the Large Organs of Patients Dying of Acute Septic Shock and Multiple Organ Failure Caused byFrontiers in cellular and infection microbiology · 2020Article
- Comparison of Pathogenicity of Invasive and Carried Meningococcal Isolates of ST-4821 Complex in China.Infection and immunity · 2019Article
- Deep mutational scanning of the Neisseria meningitidis major pilin reveals the importance of pilus tip-mediated adhesion.The EMBO journal · 2019Article
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia.
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