title: Aryl hydrocarbon receptor protects against bacterial infection by promoting macrophage survival and reactive oxygen species production.
abstract: Aryl hydrocarbon receptor (AhR) is crucial for various immune responses. The relationship between AhR and infection with the intracellular bacteria Listeria monocytogenes (LM) is poorly understood. Here, we show that in response to LM infection, AhR is required for bacterial clearance by promoting macrophage survival and reactive oxygen species (ROS) production. AhR-deficient mice were more susceptible to listeriosis, and AhR deficiency enhances bacterial growth in vivo and in vitro. On the other hand, pro-inflammatory cytokines were increased in AhR-deficient macrophages infected with LM despite enhanced susceptibility to LM infection in AhR-deficient mice. Subsequent studies demonstrate that AhR protects against macrophage cell death induced by LM infection through the induction of the antiapoptotic factor, the apoptosis inhibitor of macrophages, which promotes macrophage survival in the setting of LM infection. Furthermore, AhR promotes ROS production for bacterial clearance. Our results demonstrate that AhR is essential to the resistance against LM infection as it promotes macrophage survival and ROS production. This suggests that the activation of AhR by its ligands may be an effective strategy against listeriosis.
authors.affiliation: Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo 160-8582, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kimura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Abe
authors.forename: Sanae
authors.initials: S
authors.lastname: Tsuruta
authors.forename: Sayuri
authors.initials: S
authors.lastname: Chiba
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Takashi
authors.initials: T
authors.lastname: Sekiya
authors.forename: Rimpei
authors.initials: R
authors.lastname: Morita
authors.forename: Akihiko
authors.initials: A
authors.lastname: Yoshimura
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D058491:Bacterial Load; D002470:Cell Survival / Q000235:genetics; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D008088:Listeriosis / Q000276:immunology*; D017737:Macrophages, Peritoneal / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017382:Reactive Oxygen Species / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D017382:Reactive Oxygen Species; D018336:Receptors, Aryl Hydrocarbon
keywords: Listeria monocytogenes; apoptosis inhibitor of macrophages; dioxin receptor; innate immunity