title: Cell-wall deficient L. monocytogenes L-forms feature abrogated pathogenicity.
abstract: Stable L-forms are cell wall-deficient bacteria which are able to multiply and propagate indefinitely, despite the absence of a rigid peptidoglycan cell wall. We investigated whether L-forms of the intracellular pathogen L. monocytogenes possibly retain pathogenicity, and if they could trigger an innate immune response. While phagocytosis of L. monocytogenes L-forms by non-activated macrophages sometimes resulted in an unexpected persistence of the bacteria in the phagocytes, they were effectively eliminated by IFN-γ preactivated or bone marrow-derived macrophages (BMM). These findings were in line with the observed down-regulation of virulence factors in the cell-wall deficient L. monocytogenes. Absence of Interferon-β (IFN-β) triggering indicated inability of L-forms to escape from the phagosome into the cytosol. Moreover, abrogated cytokine response in MyD88-deficient dendritic cells (DC) challenged with L. monocytogenes L-forms suggested an exclusive TLR-dependent host response. Taken together, our data demonstrate a strong attenuation of Listeria monocytogenes L-form pathogenicity, due to diminished expression of virulence factors and innate immunity recognition, eventually resulting in elimination of L-form bacteria from phagocytes.
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich (ETHZ) Zurich, Switzerland.
authors.forename: Barbara
authors.initials: B
authors.lastname: Schnell
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich (ETHZ) Zurich, Switzerland.
authors.forename: Titu
authors.initials: T
authors.lastname: Staubli
authors.affiliation: School of Life Sciences, The Global Health Institute, Swiss Federal Institute of Technology Lausanne (EPFL) Lausanne, Switzerland.
authors.forename: Nicola L
authors.initials: NL
authors.lastname: Harris
authors.affiliation: Division of Gastroenterology and Hepatology, University Hospital Zurich Zurich, Switzerland.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Rogler
authors.affiliation: Department of Biology, Institute of Molecular Health Sciences, Swiss Federal Institute of Technology Zurich (ETHZ) Zurich, Switzerland.
authors.forename: Manfred
authors.initials: M
authors.lastname: Kopf
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich (ETHZ) Zurich, Switzerland.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Loessner
authors.affiliation: Department of Health Sciences and Technology, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zurich (ETHZ) Zurich, Switzerland.
authors.forename: Markus
authors.initials: M
authors.lastname: Schuppler
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015536:Down-Regulation; D007740:L Forms / Q000276:immunology / Q000472:pathogenicity*; D008089:Listeria monocytogenes / Q000276:immunology / Q000472:pathogenicity*; D008264:Macrophages / Q000382:microbiology*; D008810:Mice, Inbred C57BL; D010588:Phagosomes / Q000276:immunology / Q000382:microbiology; D014774:Virulence; D037521:Virulence Factors / Q000096:biosynthesis
chemical_list: D037521:Virulence Factors
keywords: L-forms; L. monocytogenes; innate immunity; pathogenicity; virulence genes