Listeria species escape from the phagosomes of interleukin-4-deactivated human macrophages independent of listeriolysin.
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.
Neumann
Katja
K
Medical Clinic B Research Unit, Department of Medicine, University Hospital, Division of Cell Biology, Institute of Anatomy, University of Zürich, Zürich, Switzerland.
Eppler
Elisabeth
E
Filgueira
Luis
L
Groscurth
Peter
P
Gasal
Eduard
E
Schaffner
Andreas
A
Schoedon
Gabriele
G
Schneemann
Markus
M
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
D000900:Anti-Bacterial Agents; D001427:Bacterial Toxins; D006360:Heat-Shock Proteins; D006460:Hemolysin Proteins; D015847:Interleukin-4; C038705:hlyA protein, Listeria monocytogenes