ArticleInfection and immunity2014
Human lung tissue explants reveal novel interactions during Legionella pneumophila infections.
Article in Infection and immunity, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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42 citing papers in PubMed, 76 citations in OpenAlex.
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- Differential transcriptomic host responses in the early phase of viral and bacterial infections in human lung tissue explants ex vivo.Respiratory research · 2024Article
- Variations in mechanical stiffness alter microvascular sprouting and stability in a PEG hydrogel model of idiopathic pulmonary fibrosis.Microcirculation (New York, N.Y. : 1994) · 2023Article
- Hiding in the yolk: A unique feature of Legionella pneumophila infection of zebrafish.PLoS pathogens · 2023Article
- Protein sociology of ProA, Mip and other secreted virulence factors at theFrontiers in cellular and infection microbiology · 2023Review
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- The role and mechanisms of gram-negative bacterial outer membrane vesicles in inflammatory diseases.Frontiers in immunology · 2023Review
- Legionella pneumophila PPIase Mip Interacts with the Bacterial Proteins SspB, Lpc2061, and FlaA and Promotes Flagellation.Infection and immunity · 2022Article
- Outer Membrane Vesicles: An Emerging Vaccine Platform.Vaccines · 2022Review
- Zinc Metalloprotease ProA fromBiomolecules · 2022Article
- Precision-cut lung slices: A powerful ex vivo model to investigate respiratory infectious diseases.Molecular microbiology · 2022Review
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- Emerging Roles of Extracellular Vesicles in Pneumococcal Infections: Immunomodulators to Potential Novel Vaccine Candidates.Frontiers in cellular and infection microbiology · 2022Review
- Bacterial Membrane Vesicles in Pneumonia: From Mediators of Virulence to Innovative Vaccine Candidates.International journal of molecular sciences · 2021Review
- Exploring the secrets of brain transcriptional regulation: developing methodologies, recent significant findings, and perspectives.Brain structure & function · 2021Review
- Ex vivo infection of murine precision-cut lung tissue slices with Mycobacterium abscessus: a model to study antimycobacterial agents.Annals of clinical microbiology and antimicrobials · 2020Article
- Gut microbiota and atherosclerosis: role of B cell for atherosclerosis focusing on the gut-immune-B2 cell axis.Journal of molecular medicine (Berlin, Germany) · 2020Review
- Choline Supplementation SensitizesInternational journal of molecular sciences · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Histological and clinical investigations describe late stages of Legionnaires' disease but cannot characterize early events of human infection. Cellular or rodent infection models lack the complexity of tissue or have nonhuman backgrounds. Therefore, we developed and applied a novel model for Legionella pneumophila infection comprising living human lung tissue. We stimulated lung explants with L. pneumophila strains and outer membrane vesicles (OMVs) to analyze tissue damage, bacterial replication, and localization as well as the transcriptional response of infected tissue. Interestingly, we found that extracellular adhesion of L. pneumophila to the entire alveolar lining precedes bacterial invasion and replication in recruited macrophages. In contrast, OMVs predominantly bound to alveolar macrophages. Specific damage to septa and epithelia increased over 48 h and was stronger in wild-type-infected and OMV-treated samples than in samples infected with the replication-deficient, type IVB secretion-deficient DotA(-) strain. Transcriptome analysis of lung tissue explants revealed a differential regulation of 2,499 genes after infection. The transcriptional response included the upregulation of uteroglobin and the downregulation of the macrophage receptor with collagenous structure (MARCO). Immunohistochemistry confirmed the downregulation of MARCO at sites of pathogen-induced tissue destruction. Neither host factor has ever been described in the context of L. pneumophila infections. This work demonstrates that the tissue explant model reproduces realistic features of Legionnaires' disease and reveals new functions for bacterial OMVs during infection. Our model allows us to characterize early steps of human infection which otherwise are not feasible for investigations.
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