title: Inhibition of meningitis-associated neutrophil apoptosis by TNF-α depends on functional PI3-kinase in monocytes.
abstract: In bacterial meningitis, neutrophils cope with bacterial infection but also lead to tissue damage. The balance of beneficial and harmful effects may depend on the lifespan of the neutrophils in the CNS. Here, we show that CSF of patients with meningococcal meningitis contains a neutrophil apoptosis-inhibiting capacity that correlates with TNF-α content. In vitro experiments show that Neisseria meningitidis as well as LPS derived from these bacteria regulated neutrophil apoptosis mainly by stimulating TNF-α production in monocytes. Whereas LPS-induced PI3K-dependent survival signals in monocytes are critical for neutrophil survival, PI3K signaling in granulocytes did not contribute to the increased lifespan of neutrophils. We conclude that LPS-driven PI3K signaling in monocytes regulates neutrophil apoptosis and thereby, may be crucial in the initiation of secondary brain damage in bacterial meningitis.
authors.affiliation: Clinical Immunology, University Hospital, Zürich, Switzerland. rechermike@bluewin.ch
authors.forename: Mike
authors.initials: M
authors.lastname: Recher
authors.forename: Ursula
authors.initials: U
authors.lastname: Malipiero
authors.forename: Dominik J
authors.initials: DJ
authors.lastname: Schaer
authors.forename: Uwe
authors.initials: U
authors.lastname: Koedel
authors.forename: Hans-Walter
authors.initials: HW
authors.lastname: Pfister
authors.forename: Thomas
authors.initials: T
authors.lastname: Birchler
authors.forename: Ulf
authors.initials: U
authors.lastname: Petrausch
authors.forename: Heike
authors.initials: H
authors.lastname: Claus
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Gast
authors.forename: Adriano
authors.initials: A
authors.lastname: Fontana
mesh_terms: D017209:Apoptosis / Q000502:physiology*; D002470:Cell Survival / Q000276:immunology; D006801:Humans; D008070:Lipopolysaccharides / Q000276:immunology / Q000494:pharmacology; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism* / Q000473:pathology*; D009000:Monocytes / Q000201:enzymology / Q000276:immunology / Q000378:metabolism*; D009504:Neutrophils / Q000166:cytology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D019869:Phosphatidylinositol 3-Kinases / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid / Q000276:immunology / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases