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Inhibition of meningitis-associated neutrophil apoptosis by TNF-  depends on functional PI3-kinase in monocytes


Recher, M; Malipiero, U; Schaer, D J; Koedel, U; Pfister, H W; Birchler, T; Petrausch, U; Claus, H; Gast, H; Fontana, A (2013). Inhibition of meningitis-associated neutrophil apoptosis by TNF- depends on functional PI3-kinase in monocytes. Journal of Leukocyte Biology, 93(2):259-266.

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.

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.

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Contributors:Department of Neurology, Ludwig-Maximilians University, Munich, Department of Neurology, Inselspital, University Hospital Berne, Institute for Hygiene and Microbiology, University of Wuerzburg
Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic and Policlinic for Internal Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Immunology
04 Faculty of Medicine > Institute of Experimental Immunology
Dewey Decimal Classification:570 Life sciences; biology
610 Medicine & health
Language:English
Date:2013
Deposited On:07 Feb 2013 11:42
Last Modified:05 Apr 2016 16:23
Publisher:Federation of American Society of Experimental Biology
ISSN:0741-5400
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1189/jlb.0511218
PubMed ID:23139429

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