title: Evidence for involvement of peptidoglycan in the triggering of an oxidative burst by Listeria monocytogenes in phagocytes.
abstract: We have shown previously that in listeric encephalitis of cattle and rats, nitrotyrosine was produced in microabscesses, implying that both superoxide anion (O(2) (-)) and nitric oxide (NO) are present and react with each other. Evidence of local synthesis of NO by macrophages was provided, but the source of O(2) (-) remained unknown. Here we have examined whether phagocytes exposed to viable and heat-killed Listeria monocytogenes (LMDelta) produce O(2) (-) and, if so, whether this results from direct interaction of phagocytes with the bacterial surface of L. monocytogenes or whether prior opsonization is required. Using lucigenin-enhanced chemiluminescence (LCL) for the measurement of O(2) (-), we show that LMDelta induces an oxidative burst in human neutrophils, monocytes and monocyte-derived macrophages (Mphi). Viability is not required, and opsonization by antibodies and/or complement does not enhance the LCL signal. As Toll-like receptors (TLR) were shown recently to mediate an oxidative burst, TLR agonists representative for pathogen-associated molecular patterns (PAMPs) were tested for their ability to elicit an oxidative burst. These included lipoteichoic acid (LTA), bacterial peptidoglycan (PGN), recombinant flagellin, CpG-containing DNA and double-stranded RNA. Only PGN and flagellin consistently elicited an LCL signal resembling that induced by LMDelta with regard to the kinetics and cell spectrum stimulated. However, flagellin was unlikely to be responsible for the LMDelta-mediated burst, as a flagellin-deficient mutant showed no decrease in LCL. We therefore assume that in LMDelta, core PGN acts as a PAMP and directly induces an oxidative burst in all phagocyte populations. We conclude that in cerebral lesions superoxide anion is generated locally by phagocytes recognizing bacterial PGN.
authors.affiliation: Institute of Veterinary Virology, University of Berne, Switzerland.
authors.forename: K A
authors.initials: KA
authors.lastname: Remer
authors.forename: T
authors.initials: T
authors.lastname: Reimer
authors.forename: M
authors.initials: M
authors.lastname: Brcic
authors.forename: T W
authors.initials: TW
authors.lastname: Jungi
mesh_terms: D005408:Flagellin / Q000378:metabolism; D006801:Humans; D008089:Listeria monocytogenes / Q000378:metabolism / Q000502:physiology*; D008163:Luminescent Measurements / Q000379:methods; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D008562:Membrane Glycoproteins / Q000378:metabolism; D009000:Monocytes / Q000378:metabolism / Q000502:physiology; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology; D009895:Opsonin Proteins / Q000378:metabolism; D010457:Peptidoglycan / Q000378:metabolism*; D010586:Phagocytes / Q000378:metabolism / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000378:metabolism; D016897:Respiratory Burst / Q000502:physiology*; D013481:Superoxides / Q000378:metabolism; D051193:Toll-Like Receptors
chemical_list: D008562:Membrane Glycoproteins; D009895:Opsonin Proteins; D010457:Peptidoglycan; D011956:Receptors, Cell Surface; D051193:Toll-Like Receptors; D013481:Superoxides; D005408:Flagellin