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

Recher, Mike; Malipiero, Ursula; Schaer, Dominik J.; Koedel, Uwe; Pfister, Hans-Walter; Birchler, Thomas; Petrausch, Ulf; Claus, Heike; Gast, Heidemarie; Fontana, Adriano (2013). Inhibition of meningitis-associated neutrophil apoptosis by TNF-α depends on functional PI3-kinase in monocytes. Journal of leukocyte biology, 93(2), pp. 259-266. Society for Leukocyte Biology 10.1189/jlb.0511218

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurology
UniBE Contributor:	Gast, Heidemarie
Subjects:	600 Technology > 610 Medicine & health
ISSN:	0741-5400
Publisher:	Society for Leukocyte Biology
Language:	English
Submitter:	Valentina Rossetti
Date Deposited:	16 Jun 2014 14:50
Last Modified:	05 Dec 2022 14:35
Publisher DOI:	10.1189/jlb.0511218
PubMed ID:	23139429
URI:	https://boris.unibe.ch/id/eprint/53489