Human lung tissue explants reveal novel interactions during Legionella pneumophila infections.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractHistological 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.
CitationHuman lung tissue explants reveal novel interactions during Legionella pneumophila infections. 2014, 82 (1):275-85 Infect. Immun.
AffiliationHelmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig, Germany.
JournalInfection and immunity
The following license files are associated with this item:
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by-nc-sa/4.0/
- PilY1 Promotes <i>Legionella pneumophila</i> Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility.
- Authors: Hoppe J, Ünal CM, Thiem S, Grimpe L, Goldmann T, Gaßler N, Richter M, Shevchuk O, Steinert M
- Issue date: 2017
- Replicative Legionella pneumophila lung infection in intratracheally inoculated A/J mice. A murine model of human Legionnaires' disease.
- Authors: Brieland J, Freeman P, Kunkel R, Chrisp C, Hurley M, Fantone J, Engleberg C
- Issue date: 1994 Dec
- Alveolar macrophages and neutrophils are the primary reservoirs for Legionella pneumophila and mediate cytosolic surveillance of type IV secretion.
- Authors: Copenhaver AM, Casson CN, Nguyen HT, Fung TC, Duda MM, Roy CR, Shin S
- Issue date: 2014 Oct
- Alveolar macrophage cell line MH-S is valuable as an in vitro model for Legionella pneumophila infection.
- Authors: Matsunaga K, Klein TW, Friedman H, Yamamoto Y
- Issue date: 2001 Mar
- Legionella pneumophila type II protein secretion promotes virulence in the A/J mouse model of Legionnaires' disease pneumonia.
- Authors: Rossier O, Starkenburg SR, Cianciotto NP
- Issue date: 2004 Jan