Fas-mediated inflammatory response in Listeria monocytogenes infection
-
1
Hyogo College of Medicine, Department of Microbiology, Japan
The molecular mechanisms of Fas (CD95/Apo-1)-mediated apoptosis are increasingly understood. However, the role of Fas-mediated production of pro-inflammatory cytokines such as IL-18 and IL-1β in bacterial infection is unclear. In this study, we demonstrate the importance of Fas-mediated signaling in IL-18/IL-1β production following infection with Listeria monocytogenes (LM). Fas-/- mice were more susceptible to LM infection than normal mice in vivo, and the elevation of IL-18 was lower in sera from Fas-/- mice infected with LM than from normal mice. In addition, IL-18/IL-1β production in LM-infected peritoneal exudate cells (PECs) from Fas-deficient mice was lower than those from Wt mice in vitro, indicating that Fas-signaling contributes to cytokine production in response to LM infection. LM infection induced Fas ligand (FasL) expression on NK cells, which stimulates Fas expressed on the infected macrophages, leading to the production of IL-18/IL-1β. This was independent of caspase-1, -11, and nucleotide-binding domain- and leucine-rich repeat-containing receptors (NLRs) such as Nlrp3 and Nlrc4, but dependent on apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc). Upon infection with LM, Wt cells exhibited caspase-8 activation, while Fas deficient cells did not. LM-induced caspase-8 activation was abrogated by inhibitor for intracellular reactive oxygen species, N-acetyl-L-cysteine (Nac). These results indicate the possibility that LM infection induced the activation of caspase-8 via Fas signaling in ROS-dependent manner, and the activated caspase-8 cleaved pro-IL-18/IL-1β to produce active cytokines. This study revealed a novel role of Fas in the induction of the inflammatory response against LM infection.
Keywords:
Fas,
IL-18,
Inflammasome,
Listeria monocytogenes,
caspase-8
Conference:
15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013.
Presentation Type:
Abstract
Topic:
Innate immunity
Citation:
Uchiyama
R and
Tsutsui
H
(2013). Fas-mediated inflammatory response in Listeria monocytogenes infection.
Front. Immunol.
Conference Abstract:
15th International Congress of Immunology (ICI).
doi: 10.3389/conf.fimmu.2013.02.00892
Copyright:
The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers.
They are made available through the Frontiers publishing platform as a service to conference organizers and presenters.
The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated.
Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed.
For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions.
Received:
19 Jun 2013;
Published Online:
22 Aug 2013.
*
Correspondence:
Dr. Ryosuke Uchiyama, Hyogo College of Medicine, Department of Microbiology, Nishinomiya, Hyogo, 663-8501, Japan, uchiyama@hyo-med.ac.jp