title: Listeria species escape from the phagosomes of interleukin-4-deactivated human macrophages independent of listeriolysin.
abstract: Listeria monocytogenes is the causative agent of infections like sepsis and meningitis, especially in immunocompromised hosts. Human macrophages are able to phagocytose and digest L. monocytogenes but IL-4 prevents human macrophages from killing the bacteria, the mechanisms of which are unknown. In the present study, we examined various listeria species and strains including wild-type and deletion mutants in human macrophages pretreated with IL-4. To analyse the IL-4-mediated deactivation process, we combined quantitative infection assays with various morphologic methods. IL-4 facilitates survival and escape of the pathogenic L. monocytogenes wild-type strain 10403S from the macrophage phagosomes. In untreated macrophages, the isogenic listeriolysin deletion mutant strain DP-L2161 was killed and did not escape from the phagolysosomes. However, after macrophage deactivation with IL-4 DP-L2161 survived and escaped from the phagosomes. This was also the case, but to a lesser extent, even for the naturally avirulent L. innocua. As detected by confocal laser-scanning fluorescence microscopy and electron microscopy, IL-4 permitted the escape of all listeria species tested, including DP-L2161 and L. innocua from the phagosomal compartment of the macrophages. We conclude that escape from the phagosome and survival of the listeria species tested in IL-4-deactivated human macrophages is independent of the virulence factor listeriolysin.
authors.affiliation: Medical Clinic B Research Unit, Department of Medicine, University Hospital, Division of Cell Biology, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
authors.forename: Katja
authors.initials: K
authors.lastname: Neumann
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Eppler
authors.forename: Luis
authors.initials: L
authors.lastname: Filgueira
authors.forename: Peter
authors.initials: P
authors.lastname: Groscurth
authors.forename: Eduard
authors.initials: E
authors.lastname: Gasal
authors.forename: Andreas
authors.initials: A
authors.lastname: Schaffner
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schoedon
authors.forename: Markus
authors.initials: M
authors.lastname: Schneemann
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001427:Bacterial Toxins / Q000235:genetics; D002470:Cell Survival; D002478:Cells, Cultured; D006360:Heat-Shock Proteins / Q000235:genetics; D006460:Hemolysin Proteins / Q000235:genetics; D006801:Humans; D015847:Interleukin-4 / Q000494:pharmacology*; D008089:Listeria monocytogenes / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D046529:Microscopy, Electron, Transmission; D010588:Phagosomes / Q000276:immunology* / Q000382:microbiology; D014774:Virulence
chemical_list: D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015847:Interleukin-4; C038705:hlyA protein, Listeria monocytogenes